ENGAGEMENT OF A T-CELL RECEPTOR BY MAJOR HISTOCOMPATIBILITY COMPLEX IRRESPECTIVE OF PEPTIDE

T cell receptors (TCR) identify target cells presenting a ligand consi sting of a major histocompatibility complex molecule (MHC) and an anti genic peptide. A considerable amount of evidence indicates that the TC R contacts both the peptide and the MHC components of the ligand. In f ully differentiated T cells the interaction between the peptide and th e TCR makes the critical contribution to eliciting a cellular response . However, during the positive selection of thymocytes the contributio n of peptide relative to MHC is less well established. Indeed it has b een suggested that the critical interaction for positive selection is between the TCR and the MHC molecule and that peptides can be viewed a s either allowing or obstructing this contact. This predicts that a gi ven TCR is capable of engaging multiple MHC/peptide complexes. In this study a system is described which detects simply engagement of the TC R by MHC/peptide complexes rather than the functional outcome of such interactions. Using this approach the extent to which peptides can inf luence contacts between the TCR and the MHC molecule has been examined . The results show that the TCR does in fact engage a wide range of li gands in an MHC-restricted but largely peptide-independent manner, sug gesting that only a few peptides are able to prevent the TCR from cont acting the MHC molecule.