The 1.5 A crystal structure of a highly selected antiviral T cell receptor provides evidence for a structural basis of immunodominance

Structure. 2002 Nov;10(11):1521-32. doi: 10.1016/s0969-2126(02)00878-x.

Abstract

Despite a potential repertoire of >10(15) alphabeta T cell receptors (TcR), the HLA B8-restricted cytolytic T cell response to a latent antigen of Epstein-Barr virus (EBV) is strikingly limited in the TcR sequences that are selected. Even in unrelated individuals this response is dominated by a single highly restricted TcR clonotype that selects identical combinations of hypervariable Valpha, Vbeta, D, J, and N region genes. We have determined the 1.5 A crystal structure of this "public" TcR, revealing that five of the six hypervariable loops adopt novel conformations providing a unique combining site that contains a deep pocket predicted to overlay the HLA B8-peptide complex. The findings suggest a structural basis for the immunodominance of this clonotype in the immune response to EBV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • DNA, Complementary / metabolism
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / immunology
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Sequence Data
  • Plasmids / metabolism
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism*

Substances

  • DNA, Complementary
  • Ligands
  • Receptors, Antigen, T-Cell

Associated data

  • PDB/1KGC