A Peptide That Antagonizes TCR-Mediated Reactions with Both Syngeneic and Allogeneic Agonists: Functional and Structural Aspects

We identify and consider some characteristics of a peptide antagonist for the Ag-specific receptor on 2C cells (the 2C TCR). The peptide, GNYSFYAL (called GNY), binds to H2K^b, and a very high-resolution crystal structure of the GNY-K^b complex at 1.35 Å is described. Although the GNY peptide does not bind to L^d, the potency of GNY-K^b as an antagonist is evident from its ability to specifically inhibit 2C TCR-mediated reactions to an allogenic agonist complex (QLSPFPFDL-L^d), as well as to a syngeneic agonist complex (SIYRYYGL-K^b). The crystal structure and the activities of alanine-substituted peptide variants point to the properties of the peptide P4 side chain and the conformation of the Tyr-P6 side chain as the structural determinants of GNYS FYAL antagonist activity.