Crossreactive T Cells spotlight the germline rules for alphabeta T cell-receptor interactions with MHC molecules.
To test whether highly crossreactive alphabeta T cell receptors (TCRs) produced during limited negative selection best illustrate evolutionarily conserved interactions between TCR and major histocompatibility complex (MHC) molecules, we solved the structures of three TCRs bound to the same MHC II peptide (IAb-3K). The TCRs had similar affinities for IAb-3K but varied from noncrossreactive to extremely crossreactive with other peptides and MHCs. Crossreactivity correlated with a shrinking, increasingly hydrophobic TCR-ligand interface, involving fewer TCR amino acids. A few CDR1 and CDR2 amino acids dominated the most crossreactive TCR interface with MHC, including Vbeta8 48Y and 54E and Valpha4 29Y, arranged to impose the familiar diagonal orientation of TCR on MHC. These interactions contribute to MHC binding by other TCRs using related V regions, but not usually so dominantly. These data show that crossreactive TCRs can spotlight the evolutionarily conserved features of TCR-MHC interactions and that these interactions impose the diagonal docking of TCRs on MHC.
Dai
Shaodong
S
Howard Hughes Medical Institute and National Jewish Medical and Research Center, Denver, CO 80206, USA.
Huseby
Eric S
ES
Rubtsova
Kira
K
Scott-Browne
James
J
Crawford
Frances
F
Macdonald
Whitney A
WA
Marrack
Philippa
P
Kappler
John W
JW
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D017124:Conserved Sequence; D003429:Cross Reactions; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D020836:Protein Structure, Quaternary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000276:immunology*; D020349:Surface Plasmon Resonance; D013601:T-Lymphocytes / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta