MHC class II-restricted presentation of the major house dust mite allergen Der p 1 Is GILT-dependent: implications for allergic asthma

PLoS One. 2013;8(1):e51343. doi: 10.1371/journal.pone.0051343. Epub 2013 Jan 11.

Abstract

Gamma-interferon-inducible lysosomal thiol reductase (GILT) is known to reduce disulfide bonds present in proteins internalized by antigen presenting cells, facilitating optimal processing and presentation of peptides on Major Histocompatibility Complex class II molecules, as well as the subsequent activation of CD4-positive T lymphocytes. Here, we show that GILT is required for class II-restricted processing and presentation of immunodominant epitopes from the major house dust mite allergen Der p 1. In the absence of GILT, CD4-positive T cell responses to Der p 1 are significantly reduced, resulting in mitigated allergic airway inflammation in response to Der p 1 and house dust mite extracts in a murine model of asthma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Antigens, Dermatophagoides / immunology*
  • Arthropod Proteins / immunology*
  • Aspartic Acid Endopeptidases / immunology
  • Asthma / immunology
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Cockroaches / immunology
  • Coculture Techniques
  • Cysteine Endopeptidases / immunology*
  • Cytokines / genetics
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Female
  • Histocompatibility Antigens Class II / immunology*
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oxidoreductases / genetics
  • Oxidoreductases / immunology*
  • Oxidoreductases / metabolism
  • Oxidoreductases Acting on Sulfur Group Donors
  • Pyroglyphidae / immunology
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • Cytokines
  • Histocompatibility Antigens Class II
  • Oxidoreductases
  • Ifi30 protein, mouse
  • Oxidoreductases Acting on Sulfur Group Donors
  • Cysteine Endopeptidases
  • Dermatophagoides pteronyssinus antigen p 1
  • Aspartic Acid Endopeptidases
  • allergen Bla g 2