Direct evidence for a functional role of HLA-DRB1 and-DRB3 gene products in the recognition of Dermatophagoides spp.(house dust mite) by helper T lymphocytes

Abstract

The contribution of the HLA-DRB1, -B3, and -B5 gene products in the recognition of Dermatophagoides spp. (house dust mite) by helper T cells isolated from an atopic individual (HLA-DRw12, DR7; DRw52b) with perennial rhinitis was investigated. Using a panel of histocompatible and histoincompatible accessory cells, the restriction specificity obtained for a long term T cell suggested that a component of the dust mite reactive repertoire recognized antigen in association with DRB3 gene products. Oligonucleotide DNA typing of the presenting cell panel demonstrated a correlation between the DRw52b allele and T cell responsiveness. Murine fibroblasts expressing DRw52b, but not DRw52a or -c molecules, presented antigen to both the T cell line and cloned T cells (DE26) derived from the line, indicating that the supertypic specificity DRw52b was able to restrict recognition of dust mite antigens. Additional T cell clones (DE9 and DE41) also isolated from the line were restricted by the products of the B1 gene locus (DRw12B1) as determined by murine fibroblasts transfected with the appropriate HLA-DR genes. Clone DE9 was degenerate in its restriction specificity, also recognizing dust mite presented by accessory cells expressing the DR2 subtypes. Presentation by fibroblasts transfected with DRw12B1, DR2Dw2B5 genes and EBV-transformed B cell lines expressing DR2DW21B1 and -B5 indicated that the functional site restricting recognition may be associated with residues 70 and 71 of the DR beta chain helical wall of the antigen combining site. Furthermore, we have recently demonstrated that both T cell clones DE9 and DE26 induce allergen dependent IgE synthesis in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

T cell subsets, epitope mapping, and HLA-restriction in patients with allergic bronchopulmonary aspergillosis.

“…It is not clear whether the dominance of clones reactive to peptides 46-65 and 106-125 is due to a relatively high affinity association of these peptides for HLA-DR2/5 or that precursor frequencies of the clones exist at higher levels in these ABPA patients due to a number of yet unidentified host determined genetic factors. Similar HLA-DR2 and DR5 restricted allergic responses to house dust mite and ragweed antigen have been reported (24)(25)(26)(27). In addition, genetic epidemiological studies and molecular analysis of HLA class II also support a strong association between DR2 and DR5 antigens and allergic responses to ragweed and grass pollen (28)(29)(30).…”

In vivo clonal dominance and limited T-cell receptor usage in human CD4+ T-cell recognition of house dust mite allergens.

“…Several epitopes derived from both the group I and II major allergens are known to be recognized by "disease-associated" T cells, namely, those that produce high levels of IL-4 and support the production of HDM-specific IgE. It has also been demonstrated that HLA-DRB1, -3, -4, and -5 gene products and DP class II molecules may restrict recognition of HDMderived T-cell determinants (31).…”

House dust mite allergy: from T‐cell epitopes to immuno‐therapy

“…Recent genetic epidemiological studies analysing IgE antibodies specific for individual proteins of HDM initially suggested that HLA-DP class TI molecules contribute to the IgE response of HDM atopic individuals, but now the association is less clear [34]. However, investigation of the restriction specificity of HDM reactive T-cells isolated from atopic individuals demonstrates the broad heterogeneity of HLA class I1 molecules capable of presenting HDM derived peptides [19,20,35 Multiple HLA class I1 specificities also appear to function as restriction elements in recognition of Der p 2 by T-cells. The extent of the heterogeneity is demonstrated by the analysis of a panel of Der p 2 specific T-cell clones all isolated from the same HDM allergic individual.…”

“…The T-cell epitopes, either alone or in the presence of APC, are able to induce antigen specific non-responsiveness by presentation of the peptides complexed with MHC class I1 molecules on the surface of the human T-cells in the absence ofcostimulatory activity. Although major HDM determinants are recognized in association with HLA-DR, -DP or -DQ gene products [19,20,21,35], T-cells using each of these restriction elements may be anergized [21,42]. This system was initially described for tolerance induction using a peptide derived from the carboxyl terminus of influenza haemagglutinin in influenza-virus immune human T-cells [46].…”