The shaping of T cell receptor recognition by self-tolerance

Immunity. 2009 Feb 20;30(2):193-203. doi: 10.1016/j.immuni.2008.11.011. Epub 2009 Jan 22.


During selection of the T cell repertoire, the immune system navigates the subtle distinction between self-restriction and self-tolerance, yet how this is achieved is unclear. Here we describe how self-tolerance toward a trans-HLA (human leukocyte antigen) allotype shapes T cell receptor (TCR) recognition of an Epstein-Barr virus (EBV) determinant (FLRGRAYGL). The recognition of HLA-B8-FLRGRAYGL by two archetypal TCRs was compared. One was a publicly selected TCR, LC13, that is alloreactive with HLA-B44; the other, CF34, lacks HLA-B44 reactivity because it arises when HLA-B44 is coinherited in trans with HLA-B8. Whereas the alloreactive LC13 TCR docked at the C terminus of HLA-B8-FLRGRAYGL, the CF34 TCR docked at the N terminus of HLA-B8-FLRGRAYGL, which coincided with a polymorphic region between HLA-B8 and HLA-B44. The markedly contrasting footprints of the LC13 and CF34 TCRs provided a portrait of how self-tolerance shapes the specificity of TCRs selected into the immune repertoire.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Viral / chemistry
  • Antigens, Viral / immunology
  • Crystallography, X-Ray
  • HLA-B8 Antigen / chemistry
  • HLA-B8 Antigen / immunology
  • Herpesvirus 4, Human / chemistry
  • Herpesvirus 4, Human / immunology
  • Humans
  • Models, Molecular
  • Peptides / chemistry
  • Peptides / immunology
  • Protein Structure, Quaternary
  • Receptors, Antigen, T-Cell / chemistry*
  • Receptors, Antigen, T-Cell / immunology*
  • Self Tolerance / immunology*
  • Structural Homology, Protein
  • Surface Plasmon Resonance


  • Antigens, Viral
  • HLA-B8 Antigen
  • Peptides
  • Receptors, Antigen, T-Cell

Associated data

  • PDB/3FFC