PEPTIDE-INDUCED NONRESPONSIVENESS OF HLA-DP RESTRICTED HUMAN T-CELLS REACTIVE WITH DERMATOPHAGOIDES SPP

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:90

Article

HIGGINS, JA ; LAMB, JR ; MARSH, SGE ; TONKS, S ; HAYBALL, JD ; ROSENBRONSON, S ; BODMER, JG ; OHEHIR, RE

关键词: PEPTIDE;    T-CELLS;    MHC;    HLA-DP;    DERMATOPHAGOIDES SPP;    HOUSE DUST MITE;    DER P-I;    DESENSITIZATION;   

DOI  :  10.1016/0091-6749(92)90098-M

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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