T-CELL RECOGNITION OF FLANKING RESIDUES OF MURINE INVARIANT CHAIN-DERIVED CLIP PEPTIDE BOUND TO MHC CLASS-II

The major site of interaction between MHC class II molecules and invar iant chain has been mapped to occupancy of the class II peptide-bindin g site by the CLIP region of invariant chain. CLIP is also seen as a d egradation product of invariant chain and can be found in association with class II as a processing intermediate. Here we analyzed the relat ive contribution of single amino acids in the murine CLIP (86-102) pep tide for binding to I-A(b) and I-A(d) and for recognition by a CLIP-sp ecific T cell hybridoma. Interestingly, the I-A(b)-restricted murine T cell hybridoma that recognizes murine CLIP peptide (86-102) is depend ent on Met 102 for activation. This amino acid is outside of the core binding region and in the CLIP/DR3 crystal structure extends outside o f the class II peptide-binding site. These data suggest that a T cell epitope presented on CLIP/class II complexes can be located predominan tly in flanking residues that extend out of the peptide binding groove of class II. (C) 1998 Academic Press.