STRUCTURAL-ANALYSIS OF TCR-LIGAND INTERACTIONS STUDIED ON H-2K(D)-RESTRICTED CLONED CTL SPECIFIC FOR A PHOTOREACTIVE PEPTIDE DERIVATIVE

To study the interaction of the TCR with its ligand, the complex of a MHC molecule and an antigenic peptide, we modified a TCR contact resid ue of a H-2K(d)-restricted antigenic peptide with photoreactive 4-azid abenzoic acid. The photoreactive group was a critical component of the epitope recognized by CTL clones derived from mice immunized with suc h a peptide derivative. The majority of these clones expressed V beta 1-encoded beta chains that were paired with J alpha TA28-encoded a cha ins. For one of these TCR, the photoaffinity labeled sites were mapped on the a chain as a J alpha TA28-encoded tryptophan and on the beta c hain as a residue of the C' strand of V beta 1. Molecular modeling of this TCR suggested the presence of a hydrophobic pocket that harbors t his tryptophan as well as a tyrosine on the C' strand of V beta 1 betw een which the photoreactive side chain inserts. It is concluded that t his avid binding principle may account for the preferential selection of V beta 1 and J alpha TA28-encoded TCR.