Identification of Dermatophagoides farinae-2-derived peptides and class II HLA molecules recognized by T cells from atopic individuals.
Der f2, the group 2 allergen of Dermatophagoides farinae, is one of the major inhalation allergens in Japan. Using the mixture of a panel of overlapping synthetic peptides that spread over the entire Der f2 molecule, we found that polyclonal Der f2-specific short-term T cell lines prepared from peripheral blood mononuclear cells of 5 individuals allergic to Der f who carry most of the common HLA haplotypes seen in the Japanese population can respond mainly to 7 different peptides. Distribution of the T cell epitopes on Der f2 was not identical with that on Der p2. Five of 7 peptides stimulated T cells of more than 2 donors, regardless of HLA types. Inhibition patterns by anti-HLA class II mAbs were heterogenous in proliferative responses of each cell line, three were mainly inhibited by anti-HLA-DR mAb, and the others were inhibited by anti-HLA-DQ mAb. One of these T cell lines, SM, of which the proliferative response was partially inhibited by anti-HLA-DQ mAb, was cloned. Indeed, the T cell clone SM4.6 was restricted by DQ6 molecules encoded for by an HLA-DRB1*1502-DRB5*0102-DQA1*0103-DQB1*0601 haplotype. These results indicate that patients' T cells recognize Der f2 in association with a variety of HLA-DR or HLA-DQ as antigen-presenting molecules. Thus, although some peptides do have a more potent T cell stimulatory activity than others, the TCR ligands formed with the Der f2 molecule are highly heterogeneous, a factor also noted in Der f1-specific T cell lines in our previous study.
Inoue
R
R
Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences, Japan.
Matsuoka
T
T
Kondo
N
N
Nishimura
Y
Y
Matsushita
S
S
D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D039741:Antigens, Dermatophagoides; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002999:Clone Cells; D000939:Epitopes; D006023:Glycoproteins / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology*; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007564:Japan; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000485:Allergens; D039741:Antigens, Dermatophagoides; D000939:Epitopes; D006023:Glycoproteins; D006681:HLA-D Antigens; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell