Structure-function relationship among T-cell receptors specific for lysozyme peptides bound to Ab or Abm-12 molecules.
The alpha beta T-cell receptor (TCR) recognizes antigenic peptides bound to major histocompatibility complex (MHC) molecules. In contrast to the antibody combining site, for which the antigen contact or complementarity-determining residues (CDRs) have been precisely defined, the location and function of the corresponding CDR regions of the alpha and beta TCR chains are not known. To develop a model system for systematic analysis of the CDRs of the alpha beta TCR, we isolated a panel of murine T-cell clones that recognize a lysozyme peptide containing residues 74-88 bound to either Ab or Abm-12 MHC class II molecules. Although these two MHC molecules differ by only three amino acid residues within the A beta chain, each of the T-cell clones was specific for peptide bound to the self-MHC molecule and did not recognize the same peptide bound to the other MHC molecule. The structural basis for this exquisite ligand specificity of the TCRs was analyzed by isolation and characterization of alpha and beta chain genes from five closely related T-cell clones. Comparison of predicted amino acid sequences mapped the ligand specificity differences to residues present within the alpha chain variable region segment and the alpha and beta chain variable-joining region junction regions. Thus with current models of TCR-ligand interactions, the results suggest that residues 26-30 of the alpha chain variable region may constitute one of the CDR regions of the TCR.
Kobori
J A
JA
Division of Biology, California Institute of Technology, Pasadena 91125.
Hood
L
L
Shastri
N
N
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002999:Clone Cells; D015329:Gene Rearrangement, T-Lymphocyte; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009113:Muramidase / Q000737:chemistry / Q000276:immunology*; D010455:Peptides / Q000737:chemistry; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D009113:Muramidase