Overlapping T-cell epitopes in the group I allergen of Dermatophagoides species restricted by HLA-DP and HLA-DR class II molecules.
The induction of IgE antibodies reactive with the group I allergen of Dermatophagoides species (house dust mite [HDM]), which comprise a major component of the allergic immune response in HDM-atopic individuals, is dependent on the functional activity of specific CD4+ T cells. In this report we demonstrate that for a particular HDM-atopic individual the T-cell response to the group I allergen of Dermatophagoides pteronyssinus (Der p I) is limited to a single region (residues 101-143) of the protein. By mapping the fine antigen specificity with T-cell clones, we observed that the sequence 101-131 of Der p I contains a cluster of at least three overlapping T-cell epitopes. Analysis of the HLA class II restriction specificity of the T-cell clones revealed that the T-cell epitope, residues 110-131, was restricted by HLA-DRB1*0101. In contrast, peptide Der p I, 110-119 was recognized in association with HLA-DPB1*0402. However, the ability of cloned T cells to proliferate to the peptide Der p I, 107-119 presented by HLA-DPB1*0401, HLA-DPB1*0402, and HLA-DPB1*0501 expressing accessory cells illustrates the heterogeneity of the restriction specificity of this region of Der p I. The application of this information in the design of peptide-based immunotherapy in the management of allergic responses to HDM is discussed.
Higgins
J A
JA
Department of Immunology, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, England.
Thorpe
C J
CJ
Hayball
J D
JD
O'Hehir
R E
RE
Lamb
J R
JR
D000485:Allergens / Q000032:analysis / Q000276:immunology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D000941:Antigens / Q000032:analysis / Q000276:immunology*; D039741:Antigens, Dermatophagoides; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology; D000939:Epitopes / Q000032:analysis / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D006682:HLA-DP Antigens / Q000032:analysis / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis / Q000276:immunology*; D006801:Humans; D008925:Mites / Q000276:immunology*; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000485:Allergens; D000941:Antigens; D039741:Antigens, Dermatophagoides; D000939:Epitopes; D006023:Glycoproteins; D006682:HLA-DP Antigens; D006684:HLA-DR Antigens