ALLOREACTIVE T-CELL RECOGNITION OF MHC CLASS-I MOLECULES - THE T-CELLRECEPTOR INTERACTS WITH LIMITED REGIONS OF THE MHC CLASS-I LONG ALPHA-HELICES

T cells recognize MHC-bound peptide, suggesting that the TCR contacts surface MHC residues adjacent to bound peptide, but the extent of MHC contact is not known. T cells also may recognize peptide-induced confo rmational changes, and alloreactive T cells may recognize surface MHC structures in addition to or independent of bound peptide. Alloreactiv e T cells are not intentionally biased to recognize particular MHC-bou nd peptides and should reveal general constraints for TCR binding. To map TCR binding sites, we tested 60 HLA-B7 site-specific mutations wit h 12 alloreactive CTL clones that express different TCRs. The alloreac tive CTL clones recognize solvent-accessible residues that cluster bet ween positions 62 to 80 and 150 to 170. Thus, TCRs contact largely ove rlapping MHC structures in the alpha(1) and alpha(2) domain long alpha helices. The dimensions and location of this site are consistent with recently reported crystallographic studies of two TCR/peptide-MHC cla ss I complexes. In contrast to TCR, Abs recognize multiple discrete ep itopes that encircle the peptide binding groove and potentially encomp ass the entire surface of the MHC molecule. Our data suggest that TCRs dock with a common discrete MHC site and that recent crystallographic models are likely to be generally applicable to T cell recognition of peptide-MHC class I complexes.