Class I Histocompatibility antigen, domains alpha 1 and 2;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473  26 SHSMRYFDTAVSRPGRGEPRFISVGYVDDTQFVRFDSDAASPRGEPRAPWVEQEGPEYWDRETQKYKRQAQADRVNLRKL 105
Cdd:pfam00129   2 SHSLRYFYTAVSRPGLGEPRFIAVGYVDDTQFVRFDSDAANPRMEPRAPWIEQEGPEYWERETQIAKGNEQIFRENLRTL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 106 RGYYNQSEDGSHTLQRMFGCDLGPDGRLLRGYNQFAYDGKDYIALNEDLRSWTAADTAAQITQRKWEAAREAEQRRAYLE 185
Cdd:pfam00129  82 LGYYNQSEGGSHTLQWMYGCDVGPDGRLLRGYEQFAYDGKDYIALNEDLRSWTAADPAAQITKRKWEAAGEAERQRAYLE 161

                         170
                  ....*....|....*...
gi 1325794473 186 GTCVEWLRRYLENGKETL 203
Cdd:pfam00129 162 GECVEWLRRYLENGKETL 179

MHC_I C-terminus; This family represents the C-terminal region of the MHC class I antigen. The family is found in conjunction with pfam00129 and pfam00047.

                          10
                  ....*....|....*....
gi 1325794473 347 QAASSNSAQGSDESLIACK 365
Cdd:pfam06623  10 QAASSDSAQGSDVSLTACK 28

Class I Histocompatibility antigen, domains alpha 1 and 2;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473  26 SHSMRYFDTAVSRPGRGEPRFISVGYVDDTQFVRFDSDAASPRGEPRAPWVEQEGPEYWDRETQKYKRQAQADRVNLRKL 105
Cdd:pfam00129   2 SHSLRYFYTAVSRPGLGEPRFIAVGYVDDTQFVRFDSDAANPRMEPRAPWIEQEGPEYWERETQIAKGNEQIFRENLRTL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 106 RGYYNQSEDGSHTLQRMFGCDLGPDGRLLRGYNQFAYDGKDYIALNEDLRSWTAADTAAQITQRKWEAAREAEQRRAYLE 185
Cdd:pfam00129  82 LGYYNQSEGGSHTLQWMYGCDVGPDGRLLRGYEQFAYDGKDYIALNEDLRSWTAADPAAQITKRKWEAAGEAERQRAYLE 161

                         170
                  ....*....|....*...
gi 1325794473 186 GTCVEWLRRYLENGKETL 203
Cdd:pfam00129 162 GECVEWLRRYLENGKETL 179

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1325794473  222 EATLRCWALGFYPAEITLTWQWDGEDQTQDTELVETRPAGDGTFQKWAAVVVPS---GEEQRYTCHVQHEGLPEP 293
Cdd:smart00407   1 KATLVCLVSGFYPPDITVTWLRNGQEVTEGVSTTDPLKNSDGTYFLSSYLTVPAstwESGDVYTCQVTHEGLKEP 75

MHC_I C-terminus; This family represents the C-terminal region of the MHC class I antigen. The family is found in conjunction with pfam00129 and pfam00047.

                          10
                  ....*....|....*....
gi 1325794473 347 QAASSNSAQGSDESLIACK 365
Cdd:pfam06623  10 QAASSDSAQGSDVSLTACK 28

Class I Histocompatibility antigen, domains alpha 1 and 2;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473  26 SHSMRYFDTAVSRPGRGEPRFISVGYVDDTQFVRFDSDAASPRGEPRAPWVEQEGPEYWDRETQKYKRQAQADRVNLRKL 105
Cdd:pfam00129   2 SHSLRYFYTAVSRPGLGEPRFIAVGYVDDTQFVRFDSDAANPRMEPRAPWIEQEGPEYWERETQIAKGNEQIFRENLRTL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 106 RGYYNQSEDGSHTLQRMFGCDLGPDGRLLRGYNQFAYDGKDYIALNEDLRSWTAADTAAQITQRKWEAAREAEQRRAYLE 185
Cdd:pfam00129  82 LGYYNQSEGGSHTLQWMYGCDVGPDGRLLRGYEQFAYDGKDYIALNEDLRSWTAADPAAQITKRKWEAAGEAERQRAYLE 161

                         170
                  ....*....|....*...
gi 1325794473 186 GTCVEWLRRYLENGKETL 203
Cdd:pfam00129 162 GECVEWLRRYLENGKETL 179

Class I major histocompatibility complex (MHC) alpha chain, alpha3 immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class I alpha chain. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 209 PKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQWDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHE 288
Cdd:cd07698     3 PKVHVTHHPRSDGESTLRCWALGFYPAEITLTWQRDGEDQTQDMELVETRPNGDGTFQKWAAVVVPSGEEQRYTCHVQHE 82

                          90
                  ....*....|
gi 1325794473 289 GLPEPLTLRW 298
Cdd:cd07698    83 GLPEPLTLRW 92

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) F; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen alpha chain F (HLA-F). HLA-F, encoded by the HLA-F gene in humans, belongs to the non-classical HLA class I heavy chain paralogs. This class I molecule mainly exists as a heterodimer associated with the invariant light chain beta-2-microglobulin. HLA-F molecules can interact with both activating and inhibitory receptors on immune cells, such as NK cells, and can present a diverse panel of peptides. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 204 QRAEHPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQWDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTC 283
Cdd:cd21023     1 QRADPPKAHVAHHPISDHEATLRCWALGFYPAEITLTWQRDGEEQTQDTELVETRPAGDGTFQKWAAVVVPPGEEQRYTC 80

                          90
                  ....*....|....*...
gi 1325794473 284 HVQHEGLPEPLTLRWKPS 301
Cdd:cd21023    81 HVQHEGLPQPLILRWEQS 98

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) A; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the class Ia major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) A. The classical class I molecules (HLA-A, -B, and -C) are responsible for the presentation of endogenous antigen to CD8+ T cells. The receptor is a heterodimer, and is composed of a heavy alpha chain and smaller beta chain. The alpha chain is encoded by a variant HLA-A gene, and the beta chain (beta-2-microglobulin) is an invariant beta-2-microglobulin molecule. The beta-2-microglobulin protein is coded for by a separate region of the human genome. HLA-A2 is associated with spontaneous abortions, HIV, and Hodgkin lymphoma. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 204 QRAEHPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQWDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTC 283
Cdd:cd21027     1 QRTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGQEQRYTC 80

                          90
                  ....*....|....*
gi 1325794473 284 HVQHEGLPEPLTLRW 298
Cdd:cd21027    81 HVQHEGLPKPLTLRW 95

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of Qa-1b; member of the C1-set of Ig superfamily (IgSF) domains; The non-classical mouse MHC class I (MHC-I) molecule Qa-1b is a non-polymorphic MHC molecule with an important function in innate immunity. It binds and presents signal peptides of classical MHC-I molecules at the cell surface and, as such, act as an indirect sensor for the normal expression of MHC-I molecules. This signal peptide dominantly accommodated in the groove of Qa-1b is called Qdm, for Qa-1 determinant modifier, and its amino acid sequence AMAPRTLLL is highly conserved among mammalian species. The Qdm/Qa-1b complex serves as a ligand for the germ-line encoded heterodimeric CD94/NKG2A receptors expressed on natural killer (NK) cells and activated CD8+ T cells and transduces inhibitory signals to these lymphocytes. Thus, upon binding, Qa-1b signals NK cells not to engage in cell lysis. The molecular basis of Qa-1b function is unclear.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 204 QRAEHPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQWDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTC 283
Cdd:cd21820     1 QRSDPPKAHVTHHPRSEDEVTLRCWALGFYPADITLTWQLNGEELTQDMELVETRPAGDGTFQKWAAVVVPLGKEQYYTC 80

                          90
                  ....*....|....*..
gi 1325794473 284 HVQHEGLPEPLTLRWKP 300
Cdd:cd21820    81 HVYHEGLPEPLTLRWEP 97

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) H2Db and H2Ld; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ia major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen (HLA) H2Db and H2Ld. H-2Ld complexed with peptide QL9 (or p2Ca) and complexed with influenza virus peptide NP366-374 (ASNEN-METM), respectively are high-affinity alloantigens for the 2C T cell receptor (TCR). The a1-a2 super domains of H-2Ld, H-2Db, and H-2Kb closely superimpose. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 205 RAEHPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQWDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCH 284
Cdd:cd21018     2 RTDSPKAHVTHHPRSKGEVTLRCWALGFYPADITLTWQLNGEELTQDMELVETRPAGDGTFQKWASVVVPLGKEQNYTCR 81

                          90
                  ....*....|....
gi 1325794473 285 VQHEGLPEPLTLRW 298
Cdd:cd21018    82 VYHEGLPEPLTLRW 95

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of T10, T22, and similar proteins; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of the murine H-2T-encoded T10, T22, and similar proteins. T10 and T22 are highly related nonclassical major histocompatibility complex (MHC) class Ib proteins that bind to certain gammadelta T cell receptors (TCRs) in the absence of other components. Classical MHC class I (class Ia) molecules participate in immune responses by presenting peptide antigens to cytolytic alpha beta T cells. Many nonclassical MHC class I (class Ib) molecules have distinct antigen-binding capabilities, suggesting that they have evolved for specific tasks that are distinct from those of MHC class Ia. Members of the IgC family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, and the IgC domain is involved in oligomerization and molecular interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 205 RAEHPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQWDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCH 284
Cdd:cd21016     2 RSDPPKAHVTRHPRPEGDVTLRCWALGFYPADITLTWQKDGEELTQDMEFVETRPAGDGTFQKWAAVVVPLGKEQSYTCH 81

                          90
                  ....*....|....*.
gi 1325794473 285 VQHEGLPEPLTLRWKP 300
Cdd:cd21016    82 VYHEGLPEPLTLRWEP 97

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of Qa-2; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of QA-2. Qa-2 is a nonclassical MHC Ib antigen, which has been implicated in both innate and adaptive immune responses, as well as embryonic development. Qa-2 has an unusual peptide binding specificity in that it requires two dominant C-terminal anchor residues and is capable of associating with a substantially more diverse array of peptide sequences than other nonclassical MHC. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 209 PKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQWDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHE 288
Cdd:cd21014     5 PKAHVTHHPRSYGAVTLRCWALGFYPADITLTWQLNGEELTQDMELVETRPAGDGTFQKWASVVVPLGKEQNYTCHVNHE 84

                          90
                  ....*....|
gi 1325794473 289 GLPEPLTLRW 298
Cdd:cd21014    85 GLPEPLTLRW 94

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of RT1-Aa; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ia major histocompatibility complex (MHC) immunoglobulin domain of RT1-Aa. While most mammalian species transport these peptides into the ER via a single allele of TAP, rats have evolved different TAPs, TAP-A and TAP-B, RT1-Aa and RT1-A1c, which are associated with TAP-A and TAP-B. The rat MHC class Ia molecule RT1-Aa has the unusual capacity to bind long peptides ending in arginine, such as MTF-E, a thirteen-residue, maternally transmitted minor histocompatibility antigen. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 205 RAEHPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQWDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCH 284
Cdd:cd21015     1 RSDPPEAHVTLHPRPEGDVTLRCWALGFYPADITLTWQLNGEDLTQDMELVETRPAGDGTFQKWASVVVPLGKEQNYTCR 80

                          90
                  ....*....|....*
gi 1325794473 285 VQHEGLPEPLTLRWK 299
Cdd:cd21015    81 VEHEGLPKPLSQRWE 95

Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen H; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ib major histocompatibility complex (MHC) immunoglobulin domain of human leukocyte antigen H (HLA-H). HLA-H (also known as hereditary hemochromatosis protein; HFE) is a major histocompatibility complex (MHC) class I-like protein that is mutated in Hereditary Hemochromatosis. HFE is a protein of 343 amino acids that includes a signal peptide, an extracellular transferrin receptor-binding region (a1 and a2), an immunoglobulin-like domain (a3), a transmembrane region, and a short cytoplasmic tail. HFE binds beta-2-microglobulin to form a heterodimer expressed at the cell surface. It binds transferrin receptor (TFRC) in its extracellular alpha1-alpha2 domain. HFE plays an important part in the regulation of hepcidin expression in response to iron overload and the liver is important in the pathophysiology of HFE-associated hemochromatosis. Nine HFE splicing variants have been reported with transcripts lacking exon 2 or exon 3, or exons 2-3, 2-4, or 2-5. Diverse mutations involving HFE introns and exons discovered in persons with hemochromatosis or their family members cause or probably cause high iron phenotypes. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 209 PKTHVTHHpVSDHEATLRCWALGFYPAEITLTWQWDGED-QTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQH 287
Cdd:cd21021     5 PLVKVTHH-VTSSVTTLRCRALNYYPQNITMKWLKDKQPmDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVEH 83

                          90
                  ....*....|.
gi 1325794473 288 EGLPEPLTLRW 298
Cdd:cd21021    84 PGLDQPLIVIW 94

Immunoglobulin Constant-1 (C1)-set domain; The members here are composed of C1-set domains, classical Ig-like domains resembling the antibody constant domain. Members of the IgC1 family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, while the IgC domain is involved in oligomerization and molecular interactions. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other strands by G, F, C, and C'.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 212 HVTHHPVS-----DHEATLRCWALGFYPAEITLTWQWDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQ---RYTC 283
Cdd:cd00098     1 TVTLLPPSpeekgGGKVTLVCLVSGFYPKDITVTWLKNGVPLTSGVSTSSPVEPNDGTYSVTSSLTVPPSDWDegaTYTC 80

                          90
                  ....*....|....*
gi 1325794473 284 HVQHEGLPEPLTLRW 298
Cdd:cd00098    81 VVTHESLKSPLSKTW 95

Class Ia major histocompatibility complex (MHC) immunoglobulin domain of MIC-A and MIC-B; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class Ia major histocompatibility complex (MHC) immunoglobulin domain of MIC-A and MIC-B. MIC-A and MIC-B are homologs that serve as stress-inducible antigens on epithelial and epithelially derived cells. Both serve as ligands for the widely expressed activating immunoreceptor NKG2D, a C-type lectin-like activating immunoreceptor. MIC-B is very similar in structure to MIC-A and likely interacts with NKG2D in an analogous manner. The interdomain flexibility observed in the MIC-A structures, a feature unique to MIC proteins among MHC class I proteins and homologs, is also displayed by MIC-B, with an interdomain relationship intermediate between the two examples of MIC-A structures. Mapping sequence variations onto the structures of MIC-A and MIC-B reveals patterns completely distinct from those displayed by classical MHC class I proteins, with a number of substitutions falling on positions likely to affect interactions with NKG2D, but with other positions lying distant from the NKG2D binding sites or buried within the core of the proteins. Members of the IgC family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding and the IgC domain is involved in oligomerization and molecular interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 205 RAEHPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQWDGEDQTQDTE-LVETRPAGDGTFQKWAAVVVPSGEEQRYTC 283
Cdd:cd21017     1 RTVPPMVNVTRSEASEGNITVTCRASGFYPWNITLSWRQDGVSLSHDTQqWGDVLPDGNGTYQTWVATRICQGEEQRFTC 80

                  ....*.
gi 1325794473 284 HVQHEG 289
Cdd:cd21017    81 YMEHSG 86

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class II beta chain. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes and they are also expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain has two globular domains (N- and C-terminal) and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 209 PKTHVTHHPVsdheaTLRCWALGFYPAEITLTWQWDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHE 288
Cdd:cd05766    11 TKTGPLEHPN-----LLVCSVTGFYPAEIEVKWFRNGQEETAGVVSTELIPNGDWTFQILVMLETTPRRGDVYTCQVEHS 85

                          90
                  ....*....|.
gi 1325794473 289 GLPEPLTLRWK 299
Cdd:cd05766    86 SLQSPLTVDWR 96

Tapasin-R immunoglobulin-like domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain on Tapasin-R. Tapasin is a V-C1 (variable-constant) immunoglobulin superfamily molecule present in the endoplasmic reticulum (ER), where it links MHC class I molecules to the transporter associated with antigen processing (TAP). Tapasin-R is a tapasin-related protein that contains similar structural motifs to Tapasin, with some marked differences, especially in the V domain, transmembrane and cytoplasmic regions. The majority of Tapasin-R is located within the ER; however, there may be some expression of Tapasin-R at the cell surface. Tapasin-R lacks an obvious ER retention signal.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 218 VSDHEATLRCWALGFYPAEITLTWQWD--GEDQTQ----DTELVETRPAGDGTFQKWAAVVVPSGEEQR---YTCHVQHE 288
Cdd:cd05771    12 KPDLPQTLSCHIAGYYPLDVDVEWLREepGGSESQvsrdGVSLSSHRQSVDGTYSISSYLTLEPGTENRgatYTCRVTHV 91

                  ....*...
gi 1325794473 289 GLPEPLTL 296
Cdd:cd05771    92 SLEEPLSV 99

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of the major histocompatibility complex (MHC) class II alpha chain. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are also expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 209 PKTHV-THHPVSDHEA-TLRCWALGFYPAEITLTWQWDGEDQTQDTELVETRPAGDGTFQKWAAV-VVPSgEEQRYTCHV 285
Cdd:cd05767     3 PEVTVfPKSPVELGEPnTLICFVDNFFPPVINVTWLRNGQPVTDGVSETVFLPREDHSFRKFSYLpFTPS-EGDIYDCRV 81

                          90
                  ....*....|....
gi 1325794473 286 QHEGLPEPLTLRWK 299
Cdd:cd05767    82 EHWGLEEPLLKHWE 95

Class I major histocompatibility complex (MHC) beta-2-microglobulin; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain in beta-2-microglobulin (beta2m). Beta2m is the non-covalently bound light chain of the human class I major histocompatibility complex (MHC-I). Beta2m is structured as a beta-sandwich domain composed of two facing beta-sheets (four stranded and three stranded), that is typical of the C-type immunoglobulin superfamily. This structure is stabilized by an intramolecular disulfide bridge connecting two Cys residues in the facing beta-sheets. In vivo, MHC-I continuously exposes beta2m on the cell surface, where it may be released to plasmatic fluids, transported to the kidneys, degraded, and finally excreted.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 209 PKTHV-THHPVSDHEA-TLRCWALGFYPAEITLTWQWDGEDQTqDTELVETRPAGDGTFQ--KWAAVVVPSGEEqrYTCH 284
Cdd:cd05770     3 PKVQVySRFPAENGKPnVLNCYVSGFHPPDIEIRLLKNGVKIE-DVEQSDLSFSKDWTFYllKYTEFTPTKGDE--YACR 79

                          90
                  ....*....|....
gi 1325794473 285 VQHEGLPEPLTLRW 298
Cdd:cd05770    80 VRHNTLSEPKIYKW 93

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DP; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DP. HLA class II histocompatibility antigen, DP(W2) beta chain is a protein that in humans is encoded by the HLA-DPB1 gene. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. MHC class II molecules are encoded by three different loci, HLA-DR, -DQ, and -DP, which are about 70% similar to each other. HLA-DP is an alphabeta heterodimer cell-surface receptor. Each DP subunit (alpha-subunit, beta-subunit) is composed of a alpha-helical N-terminal domain, an IgG-like beta sheet, a membrane spanning domain, and a cytoplasmic domain. The alpha-helical domain forms the sides of the peptide binding groove. The beta sheet regions form the base of the binding groove and the bulk of the molecule as well as the inter-subunit (non-covalent) binding region. Individuals carrying the MHCII allele, HLA-DP2, are at risk for chronic beryllium disease (CBD), a debilitating inflammatory lung condition caused by the reaction of CD4 T cells to inhaled beryllium. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 209 PKTHV--THHPVSDHEATLRCWALGFYPAEITLTWQWDGEDQTqdTELVETRPA--GDGTFQKWAAVVVPSGEEQRYTCH 284
Cdd:cd21003     4 PKVNVspSKKGPLQHHNLLVCHVTDFYPGNIQVRWFLNGQEET--AGVVSTNLIhnGDWTFQILVMLEMTPQQGDVYTCQ 81

                          90
                  ....*....|....*
gi 1325794473 285 VQHEGLPEPLTLRWK 299
Cdd:cd21003    82 VEHPSLDSPVTVEWK 96

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of histocompatibility antigen (HLA) DQ and I-A; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain of human histocompatibility antigen (HLA) DQ and mouse I-A. Three genetically distinct isotypes of class II MHC molecules are found in humans (HLA-DR, HLA-DQ, and HLA-DP), and two in mice (I-E and I-A). I-A and I-E have the same basic features insofar as peptide loading and presentation, they differ in that each interacts with distinctly different sets of peptides, and in the incidence of deletion of their genes. A structural understanding of the similarities and differences between I-A and I-E may help with understanding their roles in peptide presentation and T cell activation. Mouse I-Ag7 has a genetic susceptibility to autoimmune diabetes due to its small, uncharged amino acid residue at position 57 of their beta chain which results in the absence of a salt bridge between beta 57 and Arg alpha 76, which is adjacent to the P9 pocket of the peptide-binding groove. Human HLA-DR, -DQ, and -DP are about 70% similar to each other. HLA-DQ (DQ) is a cell surface receptor protein found on antigen presenting cells. It is an alphabeta heterodimer of type MHC class II. The alpha and beta chains are encoded by two loci, HLA-DQA1 and HLA-DQB1, that are adjacent to each other on chromosome band 6p21.3. A person often produces two alpha-chain and two beta chain variants and thus 4 isoforms of DQ. HLA-DQ is involved in the autoimmune diseases celiac disease and diabetes mellitus type. DQ is one of several antigens involved in rejection of organ transplants. DQ2 is encoded by the HLA-DQB1*02 allele group. DQ6 is encoded by the HLA-DQB1*06 allele group. DQ2 beta-chains combine with alpha-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ2.2 and DQ2.5, are also encoded by the DQA1*0201 and DQA1*0501 genes, respectively. DQ6 beta-chains combine with alpha-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. For DQ6, however, cis-isoform pairing only occurs with DQ1 alpha-chains. There are many haplotypes of DQ6. Susceptibility to Leptospirosis infection was found associated with undifferentiated DQ6. DQ8 is determined by the antibody recognition of beta8 and this generally detects the gene product of DQB1*0302. DQ8 is commonly linked to autoimmune disease in the human population. DQ8 is the second most predominant isoform linked to celiac disease and the DQ most linked to Type 1 diabetes. DQ8 increases the risk for rheumatoid arthritis and is linked to the primary risk locus for RA, HLA-DR4. DR4 also plays an important role in Type 1 diabetes. DQ8 is a split antigen of the DQ3 broad antigen. MHC class II molecules play a key role in the initiation of the antigen-specific immune response. They are expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice, and induced in nonprofessional APCs, such as keratinocyctes; they are expressed on the surface of activated human T cells and on T cells from other species. MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes; these peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC, and bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 220 DHEATLRCWALGFYPAEITLTWQWDGEDQTQ---DTELVETrpaGDGTFQkwaAVVVPSGEEQR---YTCHVQHEGLPEP 293
Cdd:cd21001    17 NHHNLLVCSVTDFYPGQIKVRWFRNDQEETAgvvSTPLIRN---GDWTFQ---ILVMLEMTPQRgdvYTCHVEHPSLQSP 90

                  ....*.
gi 1325794473 294 LTLRWK 299
Cdd:cd21001    91 ITVEWR 96

Immunoglobulin light chain Constant domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) light chain constant (C) domain. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. There are five types of heavy chains (alpha, gamma, delta, epsilon, and mu), which determine the type of immunoglobulin: IgA, IgG, IgD, IgE, and IgM, respectively. In higher vertebrates, there are two types of light chain, designated kappa and lambda, which seem to be functionally identical, and can associate with any of the heavy chains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 213 VTHHPVSDHE-----ATLRCWALGFYPAEITLTWQWDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGE---EQRYTCH 284
Cdd:cd07699     4 VTIFPPSSEElssgkATLVCLINKFYPGFATVTWKVDGSTVSSGVTTSKTEQQSDNTYSMSSYLTLSSSDwnkHKVYTCE 83

                          90
                  ....*....|....*.
gi 1325794473 285 VQHEGLPEPLTLRWKP 300
Cdd:cd07699    84 VTHEGLSSTITKSFNR 99

Class I major histocompatibility complex (MHC) homolog m144; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) homolog m144 class I alpha chain. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 225 LRCWALGFYPAEITLTWqWdgEDQTQDTELVETR-------PAGDGTFQKWAAVVVPSGEEQRYTCHVQheGLPEPLTL- 296
Cdd:cd21028    21 LRCFARDYYPADLEIRW-W--KDDGGGGALPQTSkqhhdplPSGNGLYQKHIDVYVDGGLEHVYSCRVK--GIATGLELq 95

                  ....*
gi 1325794473 297 --RWK 299
Cdd:cd21028    96 ivRWK 100

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain of histocompatibility antigen (HLA) DQ and related proteins; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class II alpha chain of histocompatibility antigen (HLA) DQ. MHC class II molecules are encoded by three different loci, HLA-DR, -DQ, and -DP, which are about 70% similar to each other. HLA-DQ (DQ) is a cell surface receptor protein found on antigen presenting cells. It is an alphabeta heterodimer of type MHC class II. The alpha and beta chains are encoded by two loci, HLA-DQA1 and HLA-DQB1, that are adjacent to each other on chromosome band 6p21.3. A person often produces two alpha-chain and two beta chain variants and thus 4 isoforms of DQ. Two autoimmune diseases in which HLA-DQ is involved are celiac disease and diabetes mellitus type 1. DQ is one of several antigens involved in rejection of organ transplants. DQ8 is a split antigen of the DQ3 broad antigen. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 209 PKTHVthhpVSDHEATLRCWALGFYPAEITLTWQWDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHE 288
Cdd:cd21008     9 PKSPV----TLGQPNTLICLVDNIFPPVINITWLSNGHSVTEGVSETSFLSKSDHSFLKISYLTFLPSADDIYDCKVEHW 84

                          90
                  ....*....|.
gi 1325794473 289 GLPEPLTLRWK 299
Cdd:cd21008    85 GLDKPLLKHWE 95

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain of histocompatibility antigen (HLA) I-E; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class II alpha chain of histocompatibility antigen (HLA) I-E. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 211 THVTHHPVSDHEAT-LRCWALGFYPAEITLTWQWDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHEG 289
Cdd:cd21005     6 TVLSRSPVNLGEPNiLICFIDKFSPPVVNVTWLRNGRPVTEGVSETVFLPRDDHLFRKFHYLTFLPSTDDFYDCEVDHWG 85

                          90
                  ....*....|
gi 1325794473 290 LPEPLTLRWK 299
Cdd:cd21005    86 LEEPLRKHWE 95

Signal-regulatory protein (SIRP) immunoglobulin-like domain 3; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in Signal-Regulatory Protein (SIRP), domain 3 (C1 repeat 2). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three Immunoglobulin superfamily domains a single V-set and two C1-set IgSF domains. Their cytoplasmic tails that contain either ITIMs or transmembrane regions that have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs but also binds CD47, but with much less affinity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 209 PKTHVTHHP-VSDHEATLRCWALGFYPAEITLTWQWDG-EDQTQDTE-LVETRpagDGTF--QKWAAVVVPSGEEQ-RYT 282
Cdd:cd16085     3 PTLEVTQQPtMVWNQVNVTCQVEKFYPQRLQLTWLENGnVSRTETPStLTVNK---DGTYnwTSWLLVNVSAHREDvVLT 79

                          90
                  ....*....|
gi 1325794473 283 CHVQHEGLPE 292
Cdd:cd16085    80 CQVEHDGQPA 89

Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain of histocompatibility antigen (HLA) I-A; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class II alpha chain of histocompatibility antigen (HLA) I-A. Three genetically distinct isotypes of class II MHC molecules are found in humans (HLA-DR, HLA-DQ, and HLA-DP), and two in mice (I-E and I-A). I-A and I-E molecules have the same basic features insofar as peptide loading and presentation, although each interacts with distinctly different sets of peptides. They also differ in that there is a relatively high incidence of deletion of the I-E a gene in both inbred strains of mice as well as wild mice and the lack of the reverse situation i.e. the deletion of I-A genes. A detailed structural understanding of the similarities and differences between I-A and the paralogous I-E could help illuminate the respective roles these molecules play in peptide presentation and T cell activation. Mouse I-Ag7 has a genetic susceptibility to autoimmune diabetes due to its small, uncharged amino acid residue at position 57 of their beta chain which results in the absence of a salt bridge between beta 57 and Arg alpha 76, which is adjacent to the P9 pocket of the peptide-binding groove. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes, and they are expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway, of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain had two globular domains (N- and C-terminal), and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1325794473 224 TLRCWALGFYPAEITLTWQWDGE---DQTQDTELVETRpagDGTFQKWAAVVVPSGEEQRYTCHVQHEGLPEPLTLRW 298
Cdd:cd21006    20 TLICFVDNIFPPVINITWLRNSKsvtDGVYETSFLVNR---DHSFHKLSYLTFIPSDDDIYDCKVEHWGLEEPVLKHW 94

Signal-regulatory protein (SIRP) immunoglobulin-like domain 2; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in Signal-Regulatory Protein (SIRP), domain 2 (C1 repeat 1). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions, but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three Immunoglobulin superfamily domains, a single V-set and two C1-set IgSF domains. Their cytoplasmic tails contain either ITIMs or transmembrane regions that have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs, but also binds CD47, but with much less affinity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1325794473 221 HEATLRCWALGFYPAEITLTWQWDG-EDQTQDTELvetRPAGDG-TFQKWAAV-VVPSGEEQR--YTCHVQHEGLPEPLT 295
Cdd:cd05772    18 QTVSFTCKSHGFSPRDITLKWFKNGnELSALQTTV---FPEGDSvSYSVSSTVqVVLTKDDVHsqLTCEVAHVTLQAPLR 94

HLA class II histocompatibility antigen DO alpha; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the nonclassical MHC class II (MHCII) protein, HLA-DO, which binds HLA-DM and influences the repertoire of peptides presented by MHCII proteins. In complex with HLA-DM, HLA-DO adopts a classical MHCII structure, with alterations near the a subunit's 310 helix. HLA-DO binds to HLA-DM at the same sites implicated in MHCII interaction, and kinetic analysis showed that HLA-DO acts as a competitive inhibitor by acting as a substrate mimic. Though more remains to be elucidated about the function of HLA-DO, its unique distribution in the mammalian body namely, the exclusive expression of HLA-DO in B cells, thymic medullary epithelial cells, and dendritic cells indicate that it may be of physiological importance and has inspired further research. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1325794473 224 TLRCWALGFYPAEITLTWQWDGEDQTQDTELVETRPAGDGTFQKWAAVV-VPSGEEQrYTCHVQHEGLPEPLTLRW 298
Cdd:cd21004    20 ILICIVDNIFPPVINITWLRNGQTVTEGVAQTSFYSQPDHLFRKFHYLPfVPSAEDV-YDCKVEHWGLDRPLLRHW 94