Peptide-induced nonresponsiveness of HLA-DP restricted human T cells reactive with Dermatophagoides spp. (house dust mite).
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.
Higgins
J A
JA
Department of Immunology, St. Mary's Hospital Medical School, Imperial College of Science, London, England.
Lamb
J R
JR
Marsh
S G
SG
Tonks
S
S
Hayball
J D
JD
Rosen-Bronson
S
S
Bodmer
J G
JG
O'Hehir
R E
RE
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002472:Cell Transformation, Viral; D002999:Clone Cells; D004391:Dust; D000939:Epitopes; D006682:HLA-DP Antigens / Q000032:analysis / Q000502:physiology*; D004854:Herpesvirus 4, Human; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D008925:Mites / Q000276:immunology*; D010455:Peptides / Q000276:immunology*
D004391:Dust; D000939:Epitopes; D006682:HLA-DP Antigens; D010455:Peptides