Proteolysis of the class II-associated invariant chain generates a peptide binding site in intracellular HLA-DR molecules. Proc. Natl. Acad. Sci. USA. 1991. 88: 3150-3154

J Immunol. 2011 Aug 1;187(3):1076-80.

Abstract

HLA-DR molecules are heterodimeric transmembrane glycoproteins that associate intracellularly with a polypeptide known as the invariant (I) chain. Shortly before expression of the HLA-DR αβ dimer on the cell surface, however the I chain is removed from the intracellular αβI complex by a mechanism thought to involve proteolysis . In this report, we show that treatment of purified αβI with the cysteine proteinase cathepsin B results in the specific proteolysis of the HLA-DR-associated I chain in vitro. As a consequence of this, the I chain is removed and free αβ dimers are released from αβI. Although αβI fails to bind an immunogenic peptide, the released αβ dimers acquire the ability to bind the peptide after proteolysis of the I chain. These results suggest that the I chain inhibits immunogenic peptide binding to αβI early during intracellular transport and demonstrate that proteolysis is likely to be the in vivo mechanism of I chain removal.

Publication types

  • Biography
  • Classical Article
  • Historical Article
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, Differentiation, B-Lymphocyte / chemistry
  • Antigens, Differentiation, B-Lymphocyte / history*
  • Cell Line, Transformed
  • Endocytosis / immunology
  • HLA-DR Antigens / chemistry
  • HLA-DR Antigens / history*
  • Histocompatibility Antigens Class II / chemistry
  • Histocompatibility Antigens Class II / history*
  • History, 20th Century
  • Humans
  • Hydrolysis
  • Intracellular Fluid / chemistry
  • Intracellular Fluid / immunology*
  • Peptides / antagonists & inhibitors
  • Peptides / chemistry
  • Peptides / history*
  • Protein Binding / immunology
  • Protein Multimerization / immunology
  • Protein Transport / immunology

Substances

  • Antigens, Differentiation, B-Lymphocyte
  • HLA-DR Antigens
  • Histocompatibility Antigens Class II
  • Peptides
  • invariant chain

Personal name as subject

  • Paul A Roche
  • Peter Cresswell