Document Detail


Insights from in situ analysis of TCR-pMHC recognition: response of an interaction network.
MedLine Citation:
PMID:  23278740     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recognition of peptide presented by the major histocompatibility complex (pMHC) molecule by the T-cell receptor (TCR) determines T-cell selection, development, differentiation, fate, and function. Despite intensive studies on the structures, thermodynamic properties, kinetic rates, and affinities of TCR-pMHC interactions in the past two decades, questions regarding the functional outcome of these interactions, i.e. how binding of the αβ TCR heterodimer with distinct pMHCs triggers different intracellular signals via the adjacent CD3 components to produce different T-cell responses, remain unclear. Most kinetic measurements have used surface plasmon resonance, a three-dimensional (3D) technique in which fluid-phase receptors and ligands are removed from their cellular environment. Recently, several two-dimensional (2D) techniques have been developed to analyze molecular interactions on live T cells with pMHCs presented by surrogate antigen-presenting cells or supported planar lipid bilayers. The insights from these in situ analyses have provided a sharp contrast of the 2D network biology approach to the 3D reductionist approach and prompted rethinking of our current views of T-cell triggering. Based on these insights, we propose a mechanochemical coupled triggering hypothesis to explain why the in situ kinetic parameters differ so much from their 3D counterparts, yet correlate so much better with T-cell functional responses.
Authors:
Cheng Zhu; Ning Jiang; Jun Huang; Veronika I Zarnitsyna; Brian D Evavold
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Immunological reviews     Volume:  251     ISSN:  1600-065X     ISO Abbreviation:  Immunol. Rev.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-02     Completed Date:  2013-06-28     Revised Date:  2014-05-15    
Medline Journal Info:
Nlm Unique ID:  7702118     Medline TA:  Immunol Rev     Country:  England    
Other Details:
Languages:  eng     Pagination:  49-64     Citation Subset:  IM    
Copyright Information:
© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Communication
Histocompatibility Antigens / immunology,  metabolism*
Humans
Immunity, Cellular
Lipid Bilayers / immunology*
Major Histocompatibility Complex / immunology
Mechanotransduction, Cellular / immunology
Peptide Fragments / immunology,  metabolism*
Protein Binding
Receptor Cross-Talk
Receptors, Antigen, T-Cell / immunology,  metabolism*
Signal Transduction / immunology
Surface Plasmon Resonance
Grant Support
ID/Acronym/Agency:
K99 AG040149/AG/NIA NIH HHS; K99AG040149/AG/NIA NIH HHS; R01 GM096187/GM/NIGMS NIH HHS; R01GM096187/GM/NIGMS NIH HHS; R01NS062358/NS/NINDS NIH HHS; R01NS071518/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Histocompatibility Antigens; 0/Lipid Bilayers; 0/Peptide Fragments; 0/Receptors, Antigen, T-Cell
Comments/Corrections

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