TY - JOUR
T1 - Structure-function relationship among T-cell receptors specific for lysozyme peptides bound to Ab or Abm-12 molecules
AU - Kobori, Joan A.
AU - Hood, Leroy
AU - Shastri, Nilabh
PY - 1992
Y1 - 1992
N2 - The αβ 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 α and βTCR chains are not known. To develop a model system for systematic analysis of the CDRs of the αβ 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 Aβ 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 and βchain genes from five closely related T-cell clones. Comparison of predicted amino acid sequences mapped the ligand specificity differences to residues present within the α chain variable region segment and the α and β chain variable-joining region junction regions. Thus with current models of TCR-ligand interactions, the results suggest that residues 26-90 of the α chain variable region may constitute one of the CDR regions of the TCR.
AB - The αβ 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 α and βTCR chains are not known. To develop a model system for systematic analysis of the CDRs of the αβ 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 Aβ 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 and βchain genes from five closely related T-cell clones. Comparison of predicted amino acid sequences mapped the ligand specificity differences to residues present within the α chain variable region segment and the α and β chain variable-joining region junction regions. Thus with current models of TCR-ligand interactions, the results suggest that residues 26-90 of the α chain variable region may constitute one of the CDR regions of the TCR.
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U2 - 10.1073/pnas.89.7.2940
DO - 10.1073/pnas.89.7.2940
M3 - Article
C2 - 1313573
AN - SCOPUS:0026589557
SN - 0027-8424
VL - 89
SP - 2940
EP - 2944
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 7
ER -