Peptide-induced nonresponsiveness of HLA-DP restricted human T cells reactive with Dermatophagoides spp. (house dust mite)

Julie A. Higgins, Jonathan R. Lamb, Steven G E Marsh, Susan Tonks, John D. Hayball, Sandra Rosen-Bronson, Julia G. Bodmer, Robyn E. O'Hehir

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Abstract

The activation of CD4+ T lymphocytes, which play a central role in allergic inflammation, depends on the recognition of allergen-derived peptides in association with major histocompatibility complex class II gene products. In this report we demonstrate, at a clonal level, that a component of the T-cell repertoire reactive with Dermatophagoides spp. (house dust mite) in atopic individuals, is restricted by HLA-DP class II molecules. This supports the recent results emerging from genetic epidemiologic studies that indicate positive associations between the HLA-DP phenotype and immune responsiveness to a variety of common allergens. Our findings also reveal that the T cells restricted by HLA-DP recognize a species-specific epitope located in the group I allergen of Dermatophagoides pteronyssinus (residues 101-119). Furthermore, we report that the pretreatment of the T cells restricted by HLA-DP with the Der p I peptide renders them nonresponsive to an immunogenic challenge with house dust mite allergen, and the loss of antigen-dependent proliferation is associated with downregulation of membrane expression of the T-cell antigen receptor. The ability to functionally inactivate T cells restricted by HLA-DP, as well as those that recognize allergen in association with HLA-DR class II molecules, suggests that desensitization with allergen-derived peptides may have therapeutic potential in the management of allergic diseases irrespective of their HLA class II association.

Original languageEnglish
Pages (from-to)749-756
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume90
Issue number5
DOIs
Publication statusPublished - 1 Jan 1992
Externally publishedYes

Keywords

  • Der p I desensitization
  • Dermatophagoides spp.
  • HLA-DP
  • house dust mite
  • MHC
  • Peptide
  • T cells

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