Dermatophagoides farinae-1-derived peptides and HLA molecules recognized by T cells from atopic individuals

Der f 1, the group I allergen in Dermatophagoides farinae extracts, is a major source of inhalation allergens in Japan. Using the mixture of a panel of overlapping synthetic peptides that spread over the entire Der f 1 molecule, we found that polyclonal Der f 1-specific short-term T cell lines prepared from peripheral blood of 6 individuals allergic to Der f who carry most of the common HLA haplotypes seen in the Japanese population can respond to 16 different peptides. Eight of 16 peptides stimulated T cells of more than 2 donors, regardless of the HLA types. Proliferative responses of four T cell lines were markedly inhibited by mAb HU4 (anti-HLA-DRB1+B5), one was inhibited partially by HU11 (anti-HLA-DQ4+5+6), and one was inhibited fully by a combination of HU4, L243 (anti-HLA-DRB1+B4) and PLM16 (anti-HLA-DRB3) but only partially by each of these mAbs. One of these T cell lines, DT, of which the proliferative response was partially inhibited by HU11, was cloned. Indeed, the T cell clones were restricted by DQ6 molecules on an HLA-DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 haplotype. These results indicate that patients' T cells recognize Der f 1 in association mainly with HLA-DRA/DRB1, but that DQAI/DQB1, DRA/DRB3 and possibly DRA/DRB4 gene products also function as antigen-presenting molecules. Thus, although some peptides have a more potent T cell-stimulatory activity than others, the T cell receptor ligands formed with the Der f 1 molecule are highly heterogeneous.