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Epitope analysis of HLA-DR-restricted helper T-cell responses to Der p II, a major allergen molecule of Dermatophagoides pteronyssinus
Authors:M. Okano  T. Nagano  M. Nakada  Y. Masuda  K. Kino  H. Yasueda  Y. Nose  Y. Nishimura  N. Ohta
Affiliation:Department of Otorhinolaryngology, Okayama University Medical School, Okayama, Japan;Meiji Institute of Health Science, Odawara, Japan;Department of Clinical Research, National Sagamihara Hospital, Sagamihara, Japan;Hyogo Prefectural Blood Transfusion Center, Kobe, Japan;Division of Immunogenetics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;Department of Medical Zoology, Nagoya City University Medical School, Nagoya, Japan
Abstract:
T-cell epitopes of Der p II, a major allergen of Dermatophagoides pteronyssinus , were analyzed by using human T-cell clones. We tested 38 cloned T cells from two Japanese patients with allergic rhinitis, and identified at least two peptides (K33-T47 and 158-C73) as helper T-cell epitopes. The former epitope was shown to be restricted by HLA-DRB1* 1502, and the latter by HLA-DRB1* 0405, both of which are typical Japanese HLA-DR alleles, suggesting that those T-cell epitopes might be important for the onset of house-dust mite allergy in the Japanese population. We prepared 15 analog peptides of the HLA-DRB1* 1502-restricted 15-mer peptide. Of those 15 residues, five (F35, L37, A39, F41, and E42) were critical for the epitope activity, and three residues (F35, A39, and E42) seemed to be included in anchor motifs for HLA-DRB1* 1502. The epitope peptide was also recognized by HLA-DRB1* 1502-positive healthy donors; however, only allergic T cells showed Th2 functions. Antigen-presenting cells of nonallergic donors were able to activate allergic T cells to express Th2 function. This seemed to suggest that antigen recognition of T cells, as well as additional unknown factors which promote Th2, rather than Th1, responses, might be important for the onset of house-dust mite allergy.
Keywords:Der p II    HLA-DR    house-dust-mite allergy    synthetic peptides    T-cell epitope    Th2 cell
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