The molecular basis of TCR germline bias for MHC is surprisingly simple.
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.
Garcia
K Christopher
KC
Department of Molecular & Cellular Physiology, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA. kcgarcia@stanford.edu
Adams
Jarrett J
JJ
Feng
Dan
D
Ely
Lauren K
LK
D000818:Animals; D019672:Genes, T-Cell Receptor; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology*; D020836:Protein Structure, Quaternary; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000235:genetics / Q000276:immunology
D011948:Receptors, Antigen, T-Cell