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.
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)
O'Hehir
R E
RE
Department of Immunology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Mach
B
B
Berte
C
C
Greenlaw
R
R
Tiercy
J M
JM
Bal
V
V
Lechler
R I
RI
Trowsdale
J
J
Lamb
J R
JR
D000485:Allergens; D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics*; D059810:HLA-DR Serological Subtypes; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008925:Mites / Q000276:immunology*; D008969:Molecular Sequence Data; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000485:Allergens; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C051104:HLA-DR52 antigen