Alloreactive T cell recognition of MHC class I molecules: the T cell receptor 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 conformational changes, and alloreactive T cells may recognize surface MHC structures in addition to or independent of bound peptide. Alloreactive T cells are not intentionally biased to recognize particular MHC-bound peptides and should reveal general constraints for TCR binding. To map TCR binding sites, we tested 60 HLA-B7 site-specific mutations with 12 alloreactive CTL clones that express different TCRs. The alloreactive CTL clones recognize solvent-accessible residues that cluster between positions 62 to 80 and 150 to 170. Thus, TCRs contact largely overlapping MHC structures in the alpha1 and alpha2 domain long alpha helices. The dimensions and location of this site are consistent with recently reported crystallographic studies of two TCR/peptide-MHC class I complexes. In contrast to TCR, Abs recognize multiple discrete epitopes that encircle the peptide binding groove and potentially encompass 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.
Smith
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KD
Department of Pathology, University of Iowa College of Medicine, Iowa City 52242, USA.
Lutz
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CT
D000595:Amino Acid Sequence; D015235:HLA-B Antigens / Q000737:chemistry / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007519:Isoantigens / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017433:Protein Structure, Secondary; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism*; D012997:Solvents; D013601:T-Lymphocytes / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism
D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I; D007519:Isoantigens; D011948:Receptors, Antigen, T-Cell; D012997:Solvents