THE SPECIFICITY AND ORIENTATION OF A TCR TO ITS PEPTIDE - MHC CLASS-II LIGANDS

A T cell-mediated immune response is mainly determined by the 3-5 aa r esidues that protrude upwards from a peptide bound to an MHC molecule. Alterations of these peptide residues can diminish, eliminate or radi cally alter the signal that the T cell receives through its T cell rec eptor (TCR). We have used peptide immunizations of normal mice and mic e carrying alpha or beta chain TCR transgenes to identify three distin ct peptide contact points. One, near the carboxyl terminus of the pept ide, involves the beta chain CDR3 region; the second was centrally loc ated and interacted with both the alpha and beta chain CDR3 loops; the third was near the amino terminus of the peptide, and affected V alph a gene usage, but not the structure of CDR3 of either TCR chain. Based on these results, we propose an orientation for the TCR of this clone d line and argue for its generality.