A T cell receptor flattens a bulged antigenic peptide presented by a major histocompatibility complex class I molecule

Nat Immunol. 2007 Mar;8(3):268-76. doi: 10.1038/ni1432. Epub 2007 Jan 28.

Abstract

Plasticity of the T cell receptor (TCR) is a hallmark of major histocompatibility complex (MHC)-restricted T cell recognition. However, it is unclear whether interactions of TCR and peptide-MHC class I (pMHCI) always conform to this paradigm. Here we describe the structure of a TCR, ELS4, in its non-ligand-bound form and in complex with a prominent 'bulged' Epstein-Barr virus peptide bound to HLA-B(*)3501. This complex was atypical of previously characterized TCR-pMHCI interactions in that a rigid face of the TCR crumpled the bulged antigenic determinant. This peptide 'bulldozing' created a more featureless pMHCI determinant, allowing the TCR to maximize MHC class I contacts essential for MHC class I restriction of TCR recognition. Our findings represent a mechanism of antigen recognition whereby the plasticity of the T cell response is dictated mainly by adjustments in the MHC-bound peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • Antigens, Viral / chemistry*
  • Antigens, Viral / immunology
  • Epitopes, T-Lymphocyte / chemistry*
  • Epitopes, T-Lymphocyte / immunology
  • Flow Cytometry
  • Histocompatibility Antigens Class I / chemistry*
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Protein Structure, Quaternary
  • Receptors, Antigen, T-Cell / chemistry*
  • Receptors, Antigen, T-Cell / immunology

Substances

  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class I
  • Receptors, Antigen, T-Cell

Associated data

  • PDB/2NW2
  • PDB/2NW3
  • PDB/2NX5