The crystal structure of a T cell receptor in complex with peptide and MHC class II.
The crystal structure of a complex involving the D10 T cell receptor (TCR), 16-residue foreign peptide antigen, and the I-Ak self major histocompatibility complex (MHC) class II molecule is reported at 3.2 angstrom resolution. The D10 TCR is oriented in an orthogonal mode relative to its peptide-MHC (pMHC) ligand, necessitated by the amino-terminal extension of peptide residues projecting from the MHC class II antigen-binding groove as part of a mini beta sheet. Consequently, the disposition of D10 complementarity-determining region loops is altered relative to that of most pMHCI-specific TCRs; the latter TCRs assume a diagonal orientation, although with substantial variability. Peptide recognition, which involves P-1 to P8 residues, is dominated by the Valpha domain, which also binds to the class II MHC beta1 helix. That docking is limited to one segment of MHC-bound peptide offers an explanation for epitope recognition and altered peptide ligand effects, suggests a structural basis for alloreactivity, and illustrates how bacterial superantigens can span the TCR-pMHCII surface.
Reinherz
E L
EL
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Tan
K
K
Tang
L
L
Kern
P
P
Liu
J
J
Xiong
Y
Y
Hussey
R E
RE
Smolyar
A
A
Hare
B
B
Zhang
R
R
Joachimiak
A
A
Chang
H C
HC
Wagner
G
G
Wang
J
J
D000818:Animals; D000941:Antigens / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003207:Conalbumin / Q000737:chemistry / Q000276:immunology; D003460:Crystallization; D018360:Crystallography, X-Ray; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D006860:Hydrogen Bonding; D008024:Ligands; D051379:Mice; D008806:Mice, Inbred AKR; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D018089:Superantigens / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D000941:Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C111388:I-Ak antigen; D008024:Ligands; D009842:Oligopeptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; D003207:Conalbumin