Major histocompatibility complex determinants select T-cell receptor alpha chain variable region dominance in a peptide-specific response.
Dominant expression of T-cell receptor (TCR) alpha or beta chain variable region (V alpha or V beta) gene families has been observed in the T-cell response to some conventional peptide antigens. Current models for the interaction of TCR V region elements with different determinants of a major histocompatibility complex (MHC)-peptide complex, the normal TCR ligand, suggest that the TCR V-J junctional region (CDR3, where J is joining) is the primary contact with a peptide epitope and that other TCR V region segments may interact directly with neighboring MHC determinants. This suggests that V alpha or V beta dominance in a specific response can be MHC-selected. In this case, if related peptides bind to an MHC molecule in a similar orientation, they could select for identical V alpha or V beta dominance even if they are noncrossreactive at the level of T-cell activation. We have screened for this possibility by introducing minimal conservative substitutions in a synthetic peptide, YYEELLKYYEELLK, that is presented to T cells in association with an uncommon A beta E alpha d mixed Ia isotype. We report here that the peptide variant FFEELLKFFEELLK is noncrossreactive with YYEELLKYYEELLK but appears to preserve the same MHC binding motif since T-cell responses are restricted to the same mixed A beta E alpha isotype. Although the two peptides are noncrossreactive in either direction, the same members of the V alpha 4 gene family are dominantly expressed in T cells specific for either peptide. We conclude that the similar topography of the two MHC-peptide complexes gives functional significance to a unique A beta E alpha determinant that selects for V alpha 4 dominance.
Natarajan
K
K
Cancer Center, University of Rochester School of Medicine, NY 14642.
Burstyn
D
D
Zauderer
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D000938:Antigen-Presenting Cells / Q000276:immunology; D001483:Base Sequence; D003001:Cloning, Molecular; D003429:Cross Reactions; D004247:DNA / Q000235:genetics; D015723:Gene Library; D006239:Haplotypes; D007739:L Cells; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000906:Antibodies; D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D010455:Peptides; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D011061:Poly A; D012313:RNA; D004247:DNA