SHARED FINE SPECIFICITY BETWEEN T-CELL RECEPTORS AND AN ANTIBODY RECOGNIZING A PEPTIDE MAJOR HISTOCOMPATIBILITY CLASS-I COMPLEX/

Cytotoxic T cells recognize mosaic structures consisting of target pep tides embedded within self-major histocompatibility complex (MHC) clas s I molecules, This structure has been described in great detail for s everal peptide-MHC complexes. In contrast, how T-cell receptors recogn ize peptide-MHC complexes have been less well characterized. We have u sed a complete set of singly substituted analogs of a mouse MHC class I, K-k-restricted peptide, influenza hemagglutinin (Ha)(255-262), to a ddress the binding specificity of this MHC molecule. Using the same pe ptide-MHC complexes we determined the fine specificity of two Ha(255-2 62)-specific, K-k-restricted T cells, and of a unique antibody, pSAN, specific for the same peptide-MHC complex, Independently, a model of t he Ha(255-262)-K-k complex was generated through homology modeling and molecular mechanics refinement. The functional data and the model cor roborated each other showing that peptide residues 1, 3, 4, 6, and 7 w ere exposed on the MHC surface and recognized by the T cells. Thus, th e majority, and perhaps all, of the side chains of the non-primary anc hor residues may be available for T-cell recognition, and contribute t o the stringent specificity of T cells. A striking similarity between the specificity of the T cells and that of the pSAN antibody was found and most of the peptide residues, which could be recognized by the T cells, could also be recognized by the antibody.