The alpha 1 domain of the HLA-DR molecule is essential for high-affinity binding of the toxic shock syndrome toxin-1.
Several exoproteins from the bacterium Staphylococcus aureus are highly potent polyclonal activators of T cells in the presence of cells bearing class II antigens of the major histocompatibility complex (MHC). These toxins, including the toxic shock syndrome toxin (TSST-1), act at nanomolar concentrations, bind directly to class II molecules, and do not require the processing typical of nominal antigen. Each toxin is capable of stimulating a subpopulation of peripheral T lymphocytes bearing particular V beta sequences as part of their alpha beta T-cell receptors. It is not known how these so-called 'superantigens' bind to class II and how this binding stimulates T cells. In this study, the different affinities of TSST-1 for human class II molecules DR and DP were exploited to define the region of a class II molecule necessary for high-affinity binding. Using chimaeric alpha- and beta-chains of DR and DP expressed at the surface of transfected murine fibroblasts and a binding assay with TSST-1, it was shown that the alpha 1 domain of DR is essential for high-affinity binding, and further that TSST-1 binding did not prevent subsequent binding of a DR-restricted antigenic peptide. This is compatible with a model of superantigen making external contacts with both class II and T cell receptor, and suggests that the V beta portion of the T-cell receptor interacts with the nonpolymorphic alpha-chain of DR.
Karp
D R
DR
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Teletski
C L
CL
Scholl
P
P
Geha
R
R
Long
E O
EO
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001427:Bacterial Toxins; D001665:Binding Sites; D004274:DNA, Recombinant; D004768:Enterotoxins / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology; D005434:Flow Cytometry; D006682:HLA-DP Antigens / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007739:L Cells / Q000276:immunology; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D013329:Structure-Activity Relationship; D018089:Superantigens; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004274:DNA, Recombinant; D004768:Enterotoxins; D006682:HLA-DP Antigens; D006684:HLA-DR Antigens; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal