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

1992; Elsevier BV; Volume: 90; Issue: 5 Linguagem: Inglês

10.1016/0091-6749(92)90098-m

1097-6825

Julian P. T. Higgins, Jonathan R. Lamb, S. Marsh, Susan Tonks, John D. Hayball, Sandra Rosen‐Bronson, Jean-Luc Bodmer, Robyn E. O’Hehir,

Immune Cell Function and Interaction

The activation of CD4 + T lymphocytes, which play a central role in allergic in$ammation, 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-spec& 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 IIL.9 class II association.(J ALLERGY CLIN LUMUNOL 1992;90:749-56.)Key worak: