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 invariant chain has been mapped to occupancy of the class II peptide-binding site by the CLIP region of invariant chain. CLIP is also seen as a degradation product of invariant chain and can be found in association with class II as a processing intermediate. Here we analyzed the relative contribution of single amino acids in the murine CLIP (86–102) peptide for binding to I-Aband I-Adand for recognition by a CLIP-specific T cell hybridoma. Interestingly, the I-Ab-restricted murine T cell hybridoma that recognizes murine CLIP peptide (86–102) is dependent on Met 102 for activation. This amino acid is outside of the core binding region and in the CLIP/DR3 crystal structure extends outside of the class II peptide-binding site. These data suggest that a T cell epitope presented on CLIP/class II complexes can be located predominantly in flanking residues that extend out of the peptide binding groove of class II.