The crystal structure of a T cell receptor in complex with peptide and MHC class II

Science. 1999 Dec 3;286(5446):1913-21. doi: 10.1126/science.286.5446.1913.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens / chemistry*
  • Antigens / immunology
  • Antigens / metabolism
  • Binding Sites
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Conalbumin / chemistry
  • Conalbumin / immunology
  • Crystallization
  • Crystallography, X-Ray
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class II / chemistry*
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism
  • Hydrogen Bonding
  • Ligands
  • Mice
  • Mice, Inbred AKR
  • Models, Molecular
  • Oligopeptides / chemistry
  • Oligopeptides / immunology
  • Oligopeptides / metabolism
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Receptors, Antigen, T-Cell, alpha-beta / chemistry*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Superantigens / immunology
  • Superantigens / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / immunology

Substances

  • Antigens
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • I-Ak antigen
  • Ligands
  • Oligopeptides
  • Receptors, Antigen, T-Cell, alpha-beta
  • Superantigens
  • Conalbumin

Associated data

  • PDB/1D9K