Understanding the drivers of MHC restriction of T cell receptors

Nat Rev Immunol. 2018 Jul;18(7):467-478. doi: 10.1038/s41577-018-0007-5.


T cell discrimination of self and non-self is predicated on αβ T cell receptor (TCR) co-recognition of peptides presented by MHC molecules. Over the past 20 years, structurally focused investigations into this MHC-restricted response have provided profound insights into T cell function. Simultaneously, two models of TCR recognition have emerged, centred on whether the TCR has, through evolution, acquired an intrinsic germline-encoded capacity for MHC recognition or whether MHC reactivity is conferred by developmental selection of TCRs. Here, we review the structural and functional data that pertain to these theories of TCR recognition, which indicate that it will be necessary to assimilate features of both models to fully account for the molecular drivers of this evolutionarily ancient interaction between the TCR and MHC molecules.

Publication types

  • Historical Article
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibody Diversity
  • Evolution, Molecular
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class II / chemistry
  • Histocompatibility Antigens Class II / genetics
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Immunogenetics / history
  • Major Histocompatibility Complex*
  • Models, Genetic
  • Models, Immunological
  • Models, Molecular
  • Receptors, Antigen, T-Cell / chemistry
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / immunology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Systems Biology
  • T-Lymphocytes / immunology


  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Receptors, Antigen, T-Cell