Four A6-TCR/peptide/HLA-A2 structures that generate very different T cell signals are nearly identical

The interactions of three singly substituted peptide variants of the HTLV-1 Tax peptide bound to HLA-A2 with the A6 T cell receptor have been studied using T cell assays, kinetic and thermodynamic measurements, and X-ray crys tallography. The three peptide/MHC ligands include weak agonists and antago nists with different affinities for TCR. The three-dimensional structures o f the three A6-TCR/peptide/HLA-A2 complexes are remarkably similar to each other and to the wild-type agonist complex, with minor adjustments at the i nterface to accommodate the peptide substitutions (P6A, V7R, and Y8A). The lack of correlation between structural changes and the type of T cell signa ls induced provides direct evidence that different signals are not generate d by different ligand-induced conformational changes in the alpha beta TCR.