Evolutionarily conserved amino acids that control TCR-MHC interaction.
The rules for the conserved reaction of alphabeta T cell receptors (TCRs) with major histocompatibility complex (MHC) proteins plus peptides are poorly understood, probably because thymocytes bearing TCRs with the strongest MHC reactivity are lost by negative selection. Thus, only TCRs with an attenuated ability to react with MHC appear on mature T cells. Also, the interaction sites between TCRs and MHC may be inherently flexible and hence difficult to spot. We reevaluated contacts between TCRs and MHC in the solved structures of their complexes with these points in mind. Relatively conserved amino acids in the TCR complementarity-determining regions (CDR) 1 and CDR2 are often used to bind exposed areas of the MHC alpha-helices. These areas are exposed because of small amino acids that allow somewhat flexible binding of the TCRs. The TCR amino acids involved are specific to families of variable (V) regions and to some extent different rules may govern the recognition of MHCI versus MHCII.
Marrack
Philippa
P
Howard Hughes Medical Institute, University of Colorado Denver Health Science Center, Denver, Colorado 80206, USA. marrackp@njc.org
Scott-Browne
James P
JP
Dai
Shaodong
S
Gapin
Laurent
L
Kappler
John W
JW
D000596:Amino Acids / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D006649:Histocompatibility Antigens / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D000596:Amino Acids; D022801:Complementarity Determining Regions; D006649:Histocompatibility Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta