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Structure-function relationship among T-cell receptors specific for lysozyme peptides bound to A^b or A^(bm-12) molecules

Kobori, Joan A. and Hood, Leroy and Shastri, Nilabh (1992) Structure-function relationship among T-cell receptors specific for lysozyme peptides bound to A^b or A^(bm-12) molecules. Proceedings of the National Academy of Sciences of the United States of America, 89 (7). pp. 2940-2944. ISSN 0027-8424. PMCID PMC48779. doi:10.1073/pnas.89.7.2940.

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The ɑβ 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 ɑ and β TCR chains are not known. To develop a model system for systematic analysis of the CDRs of the ɑβ TCR, we isolated a panel of murine T-cell clones that recognize a lysozyme peptide containing residues 74-88 bound to either A^b or A^(bm-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 ɑ and β 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 ɑ chain variable region segment and the ɑ and β chain variable-joining region junction regions. Thus with current models of TCR-ligand interactions, the results suggest that residues 26-30 of the ɑ chain variable region may constitute one of the CDR regions of the TCR.

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Hood, Leroy0000-0001-7158-3678
Additional Information:© 1992 National Academy of Sciences. Contributed by Leroy Hood, December 18, 1991. We thank Ms. C. Davis, E. Saffman and C. Tong for their excellent technical assistance and Dr. S. Horvath for the synthesis of peptides and oligonucleotides. We are grateful to Dr. R. Germain for the gift of FT7.1 and FIf7.2 L-cell transfectants. We thank Drs. R. Barth, P. Bjorkman, C. Readhead, I. Stroynowski, A. Winoto, and T. J. Yoo for comments on the manuscript. This work was supported in part by National Institutes of Health Grants A126604 and A122274 to N.S. and L.H., respectively. N.S. is a scholar of the Pew Biomedical Foundation.
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Pew Biomedical FoundationUNSPECIFIED
Issue or Number:7
PubMed Central ID:PMC48779
Record Number:CaltechAUTHORS:20141216-135524864
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Official Citation:J A Kobori, L Hood, and N Shastri Structure-function relationship among T-cell receptors specific for lysozyme peptides bound to Ab or Abm-12 molecules PNAS 1992 89 (7) 2940-2944
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52888
Deposited By: Ruth Sustaita
Deposited On:16 Dec 2014 22:18
Last Modified:10 Nov 2021 19:44

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