Overlapping T-cell epitopes in the group I allergen of Dermatophagoides species restricted by HLA-DP and HLA-DR class II molecules

Abstract

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.