Four A6-TCR/peptide/HLA-A2 structures that generate very different T cell signals are nearly identical.
The interactions of three singly substituted peptide variants of the HTLV-1 Tax peptide bound to HLA-A2 with the A6 T cell receptor have been studied using T cell assays, kinetic and thermodynamic measurements, and X-ray crystallography. The three peptide/MHC ligands include weak agonists and antagonists with different affinities for TCR. The three-dimensional structures of the three A6-TCR/peptide/HLA-A2 complexes are remarkably similar to each other and to the wild-type agonist complex, with minor adjustments at the interface to accommodate the peptide substitutions (P6A, V7R, and Y8A). The lack of correlation between structural changes and the type of T cell signals induced provides direct evidence that different signals are not generated by different ligand-induced conformational changes in the alphabeta TCR.
Ding
Y H
YH
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Baker
B M
BM
Garboczi
D N
DN
Biddison
W E
WE
Wiley
D C
DC
D019943:Amino Acid Substitution / Q000276:immunology; D016356:Gene Products, tax / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology; D015789:HLA-A2 Antigen / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008285:Major Histocompatibility Complex / Q000502:physiology; D010455:Peptides / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D013499:Surface Properties; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D013816:Thermodynamics
D016356:Gene Products, tax; D015789:HLA-A2 Antigen; D046911:Macromolecular Substances; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta