title: The crystal structure of a T cell receptor in complex with peptide and MHC class II.
abstract: 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.
authors.affiliation: Laboratory of Immunobiology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: E L
authors.initials: EL
authors.lastname: Reinherz
authors.forename: K
authors.initials: K
authors.lastname: Tan
authors.forename: L
authors.initials: L
authors.lastname: Tang
authors.forename: P
authors.initials: P
authors.lastname: Kern
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Xiong
authors.forename: R E
authors.initials: RE
authors.lastname: Hussey
authors.forename: A
authors.initials: A
authors.lastname: Smolyar
authors.forename: B
authors.initials: B
authors.lastname: Hare
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Joachimiak
authors.forename: H C
authors.initials: HC
authors.lastname: Chang
authors.forename: G
authors.initials: G
authors.lastname: Wagner
authors.forename: J
authors.initials: J
authors.lastname: Wang
mesh_terms: 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
chemical_list: 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