Document Detail


The structural basis of αβ T-lineage immune recognition: TCR docking topologies, mechanotransduction, and co-receptor function.
MedLine Citation:
PMID:  23046125     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Self versus non-self discrimination is at the core of T-lymphocyte recognition. To this end, αβ T-cell receptors (TCRs) ligate 'foreign' peptides bound to major histocompatibility complex (MHC) class I or class II molecules (pMHC) arrayed on the surface of antigen-presenting cells (APCs). Since the discovery of TCRs approximately 30 years ago, considerable structural and functional data have detailed the molecular basis of their extraordinary ligand specificity and sensitivity in mediating adaptive T-cell immunity. This review focuses on the structural biology of the Fab-like TCRαβ clonotypic heterodimer and its unique features in conjunction with those of the associated CD3εγ and CD3εδ heterodimeric molecules, which, along with CD3ζζ homodimer, comprise the TCR complex in a stoichiometry of 1:1:1:1. The basis of optimized TCRαβ docking geometry on the pMHC linked to TCR mechanotransduction and required for T-cell signaling as well as CD4 and CD8 co-receptor function is detailed. A model of the TCR ectodomain complex including its connecting peptides suggests how force generated during T-cell immune surveillance and at the immunological synapse results in dynamic TCR quaternary change involving its heterodimeric components. Potential insights from the structural biology relevant to immunity and immunosuppression are revealed.
Authors:
Jia-huai Wang; Ellis L Reinherz
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Immunological reviews     Volume:  250     ISSN:  1600-065X     ISO Abbreviation:  Immunol. Rev.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-10     Completed Date:  2013-02-25     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  7702118     Medline TA:  Immunol Rev     Country:  England    
Other Details:
Languages:  eng     Pagination:  102-19     Citation Subset:  IM    
Copyright Information:
© 2012 John Wiley & Sons A/S.
Affiliation:
Laboratory of Immunobiology, Dana-Farber Cancer Institute and Departments, Harvard Medical School, Boston, MA, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigen-Presenting Cells / cytology,  immunology,  metabolism
Antigens / chemistry*,  immunology,  metabolism
Antigens, CD3 / chemistry*,  immunology,  metabolism
CD4-Positive T-Lymphocytes / cytology,  immunology,  metabolism
CD8-Positive T-Lymphocytes / cytology,  immunology,  metabolism
Humans
Major Histocompatibility Complex / immunology*
Mechanotransduction, Cellular
Mice
Models, Molecular
Peptides / chemistry*,  immunology,  metabolism
Protein Conformation
Protein Multimerization
Receptors, Antigen, T-Cell, alpha-beta / chemistry*,  immunology,  metabolism
Grant Support
ID/Acronym/Agency:
P01 HL048675/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens; 0/Antigens, CD3; 0/CD3E protein, human; 0/Peptides; 0/Receptors, Antigen, T-Cell, alpha-beta
Comments/Corrections

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