Document Detail


A structural voyage toward an understanding of the MHC-I-restricted immune response: lessons learned and much to be learned.
MedLine Citation:
PMID:  23046123     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
T cells that express clonally distributed αβ T-cell receptors (TCRs) corecognize antigenic peptides (p) bound to major histocompatibility complex class I (MHC-I) and class II molecules (MHC-II). Extensive human leukocyte antigen (HLA) polymorphism enables HLA molecules from different haplotypes to capture an array of self- and microbe-derived peptide antigens that is fundamental to adaptive immunity. T cells developing in the thymus are selected for weak binding to self-peptide-HLA complexes generating a vast repertoire of clonally distinct T cells in the periphery. Indeed, diversity within germline loci and the finally assembled TCR genes, coupled with inherent TCR cross-reactivity, enables CD8(+) T cells to survey the multitude of pHLA-I landscapes. Precisely how does the TCR ligate to pHLA-I, and how does knowledge of the detailed structural interactions inform immunobiology? A recent number of our structural studies concerning the TCR-pMHC-I axis, alongside others in the field, have provided insight into HLA-I polymorphism, pMHC-I flexibility, TCR bias, TCR polymorphism, maintenance of self-tolerance, T-cell cross-reactivity, and alloreactivity. Collectively, the data also provide an opportunity to address the structural correlates of MHC-I restriction. Here, we provide our perspective concerning these advances in the field. Although much key information has been gleaned, the structural data show that some of the key concepts surrounding the TCR-pMHC-I interaction remain controversial and unresolved.
Authors:
Stephanie Gras; Scott R Burrows; Stephen J Turner; Andrew K Sewell; James McCluskey; Jamie Rossjohn
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; 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:  2014-11-05    
Medline Journal Info:
Nlm Unique ID:  7702118     Medline TA:  Immunol Rev     Country:  England    
Other Details:
Languages:  eng     Pagination:  61-81     Citation Subset:  IM    
Copyright Information:
© 2012 John Wiley & Sons A/S.
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MeSH Terms
Descriptor/Qualifier:
Adaptive Immunity
Animals
Binding Sites
Cross Reactions
HLA Antigens / chemistry*,  immunology,  metabolism
Histocompatibility Antigens Class I / chemistry*,  immunology,  metabolism
Humans
Major Histocompatibility Complex / immunology*
Mice
Models, Molecular
Peptides / chemistry*,  immunology,  metabolism
Protein Binding
Protein Conformation
Receptors, Antigen, T-Cell, alpha-beta / chemistry*,  immunology,  metabolism
T-Lymphocytes / cytology,  immunology*,  metabolism
Grant Support
ID/Acronym/Agency:
BB/H001085/1//Biotechnology and Biological Sciences Research Council
Chemical
Reg. No./Substance:
0/HLA Antigens; 0/Histocompatibility Antigens Class I; 0/Peptides; 0/Receptors, Antigen, T-Cell, alpha-beta

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