The molecular mechanism by which the superantigen that causes Toxic Shock Syndrome, TSST-l, binds to human class II histocompatibility antigen and T-cell receptors will be studied by high resolution X-ray crystallography. A complex between a soluble form of the class II MHC molecule HLA-DR1 will be crystallized in complex with TSST-l and selected subfragments. A soluble form of alpha-beta T-cell receptor (TCR) that interacts with TSST- l will be constructed and attempts made to form and to crystallize the ternary complex DR1:TSST-1:TCR. A strategy is also proposed for discovering and constructing a soluble form of a gamma-delta TCR that interacts with TSST-1. If successful, this might allow the structure determination of a gamma-delta TCR in an active complex (DR1:TSST-1: gamma-delta TCR).
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