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Nat Immunol. 2009 Feb;10(2):143-7. doi: 10.1038/ni.f.219.

The molecular basis of TCR germline bias for MHC is surprisingly simple.

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  • 1Department of Molecular & Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA. kcgarcia@stanford.edu


The elusive etiology of germline bias of the T cell receptor (TCR) for major histocompatibility complex (MHC) has been clarified by recent 'proof-of-concept' structural results demonstrating the conservation of specific TCR-MHC interfacial contacts in complexes bearing common variable segments and MHC allotypes. We suggest that each TCR variable-region gene product engages each type of MHC through a 'menu' of structurally coded recognition motifs that have arisen through coevolution. The requirement for MHC-restricted T cell recognition during thymic selection and peripheral surveillance has necessitated the existence of such a coded recognition system. Given these findings, a reconsideration of the TCR-peptide-MHC structural database shows that not only have the answers been there all along but also they were predictable by the first principles of physical chemistry.

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