Human gammadelta T cells expressing the Vgamma2Vdelta2 antigen receptors recognize nonpeptide prenyl pyrophosphate and alkylamine antigens. We find that they also recognize staphylococcal enterotoxin A superantigens in a manner distinct from the recognition of nonpeptide antigens. Using chimeric and mutant toxins, SEA amino acid residues 20-27 were shown to be required for gammadelta TCR recognition of SEA. Residues at 200-207 that are critical for specific alphabeta TCR recognition of SEA do not affect gammadelta TCR recognition. SEA residues 20-27 are located in an area contiguous with the binding site of V beta chains. This study defines a superantigen recognition site for a gammadelta T cell receptor and demonstrates the differences between Vgamma2Vdelta2+ T cell recognition of superantigens and nonpeptide antigens.
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