Identification of a common docking topology with substantial variation among different TCR-peptide-MHC complexes.
Whether T-cell receptors (TCRs) recognize antigenic peptides bound to major histocompatability complex (MHC) molecules through common or distinct docking modes is currently uncertain. We report the crystal structure of a complex between the murine N15 TCR [1-4] and its peptide-MHC ligand, an octapeptide fragment representing amino acids 52-59 of the vesicular stomatitis virus nuclear capsid protein (VSV8) bound to the murine H-2Kb class I MHC molecule. Comparison of the structure of the N15 TCR-VSV8-H-2Kb complex with the murine 2C TCR-dEV8-H-2Kb [5] and the human A6 TCR-Tax-HLA-A2 [6] complexes revealed a common docking mode, regardless of TCR specificity or species origin, in which the TCR variable Valpha domain overlies the MHC alpha2 helix and the Vbeta domain overlies the MHC alpha1 helix. As a consequence, the complementary determining regions CDR1 and CDR3 of the TCR Valpha and Vbeta domains make the major contacts with the peptide, while the CDR2 loops interact primarily with the MHC. Nonetheless, in terms of the details of the relative orientation and disposition of binding, there is substantial variation in TCR parameters, which we term twist, tilt and shift, and which define the variation of the V module of the TCR relative to the MHC antigen-binding groove.
Teng
M K
MK
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Smolyar
A
A
Tse
A G
AG
Liu
J H
JH
Liu
J
J
Hussey
R E
RE
Nathenson
S G
SG
Chang
H C
HC
Reinherz
E L
EL
Wang
J H
JH
D000818:Animals; D001665:Binding Sites; D002213:Capsid / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D016356:Gene Products, tax / Q000737:chemistry / Q000378:metabolism; D006183:H-2 Antigens / Q000737:chemistry / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000378:metabolism; D006649:Histocompatibility Antigens / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D051379:Mice; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000737:chemistry / Q000378:metabolism
D016356:Gene Products, tax; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015789:HLA-A2 Antigen; D006649:Histocompatibility Antigens; D046911:Macromolecular Substances; D009842:Oligopeptides; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta