Document Detail

T cells and their eons-old obsession with MHC.
MedLine Citation:
PMID:  23046122     Owner:  NLM     Status:  MEDLINE    
T cells bearing receptors made up of α and β chains (TCRs) usually react with peptides bound to major histocompatibility complex proteins (MHC). This bias could be imposed by positive selection, the phenomenon that selects thymocytes to mature into T cells only if the TCRs they bear react with low but appreciable affinity with MHC + peptide combinations in the thymus cortex. However, it is also possible that the polypeptides of TCRs themselves do not have random specificities but rather are biased toward reaction with MHC. Evolution would therefore have selected for a collection of TCR variable elements that are prone to react with MHC. If this were to be so, positive selection would act on thymocytes bearing a pre biased collection of TCRs to pick out those that react to some extent, but not too well, with self MHC + self-peptides. A problem with studies of this evolutionary idea is the fact that there are many TCR variable elements and that these differ considerably in the amino acids with which they contact MHC. However, recent experiments by our group and others suggest that one group of TCR variable elements, those related to the mouse Vβ8 family, has amino acids in their CDR2 regions that consistently bind a particular site on an MHC α-helix. Other groups of variable elements may use different patterns of amino acids to achieve the same goal. Mutation of these amino acids reduces the ability of T cells and thymocytes to react with MHC. These amino acids are present in the variable regions of distantly related species such as sharks and human. Overall the data indicate that TCR elements have indeed been selected by evolution to react with MHC proteins. Many mysteries about TCRs remain to be solved, including the nature of auto-recognition, the basis of MHC allele specificity, and the very nature and complexity of TCRs on mature T cells.
Lei Yin; James Scott-Browne; John W Kappler; Laurent Gapin; Philippa Marrack
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:  2014-03-27    
Medline Journal Info:
Nlm Unique ID:  7702118     Medline TA:  Immunol Rev     Country:  England    
Other Details:
Languages:  eng     Pagination:  49-60     Citation Subset:  IM    
Copyright Information:
© 2012 John Wiley & Sons A/S.
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MeSH Terms
Antigens / chemistry*,  immunology,  metabolism
Binding Sites
Cross Reactions
Major Histocompatibility Complex / immunology*
Models, Molecular
Peptides / chemistry*,  immunology,  metabolism
Protein Binding
Protein Conformation
Receptors, Antigen, T-Cell, alpha-beta / chemistry*,  immunology,  metabolism
T-Lymphocytes / cytology,  immunology*,  metabolism
Thymocytes / cytology,  immunology*
Thymus Gland
Grant Support
AI-076463/AI/NIAID NIH HHS; AI-078246/AI/NIAID NIH HHS; AI-18785/AI/NIAID NIH HHS; AI-22295/AI/NIAID NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Antigens; 0/Peptides; 0/Receptors, Antigen, T-Cell, alpha-beta

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