<i>Dermatophagoides farinae</i>-1-Derived Peptides and HLA Molecules Recognized by T Cells from Atopic Individuals

Abstract

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 HUH, 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 DQA1/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.

Identification of β‐lactoglobulin‐derived peptides and class II HLA molecules recognized by T cells from patients with milk allergy

“…Among these T cell epitopes, only residues 77–97 were commonly recognized by human T cells in the current study. Several investigators have reported a variety of T cell epitopes for each antigen [1–10], and our data also show heterogeneity of T cell epitopes on BLG. HLA types are apparently distinct in different ethnic groups, and as demonstrated in the current literature on other allergic diseases, they indeed function as BLG‐presenting molecules.…”

“…The CD4 + helper T cells (Th) are activated upon recognition of these peptide‐MHC complexes by T cell receptor (TCR) molecules and exert effector functions through various biological activities of the secreted lymphokines. The T cell epitopes of several major allergens have been reported [1–10]. However, little has been reported on T cell epitopes recognize food antigens.…”

Ligation of HLA-DR Molecules on B Cells Induces Enhanced Expression of IgM Heavy Chain Genes in Association with Syk Activation

“…Engagement of class II molecules on the THP-1 monocyte cell line with staphylococcal enterotoxin A induced IL-1␤ and tumor necrosis factor-␣ (40). Our previous studies demonstrated that certain T cell-monocyte interactions, via altered TCR ligands, affect monocyte responses to produce IL-12 (p70), which leads to specific up-regulation of interferon-␥ production from T cells (1). Moreover, we recently observed that cross-linking class II HLA molecules on monocytes induces a wide variety of monokine production (41), which is accompanied by activation of signaling molecules.…”

“…We earlier reported that interactions between a T cell clone and monocyte via altered T cell receptor (TCR) 1 ligands, affect monocyte responses to produce IL-12, events which lead to specific up-regulation of interferon-␥ production from T cells (1). Thus, signals transmitted to monocytes via HLA molecules are involved in determining immune response patterns.…”

Interaction among human leucocyte antigen–peptide–T cell receptor complexes in cow's milk allergy: the significance of human leucocyte antigen and T cell receptor–complementarity determining region 3 loops

“…The CD4 + T helper cells are activated upon recognition of these peptide‐HLA complexes by TCR molecules and exert effector functions through various biological activities of the secreted lymphokines. T cell epitopes of several major allergens have been reported [1–10]. Although little information has been reported on T cell epitopes that recognize food antigens, we identified T cell epitopes and antigen‐presenting molecules recognized by T cells from patients with cow's milk allergy [11].…”