Understanding the drivers of MHC restriction of T cell receptors

Nicole L. La Gruta, Stephanie Gras, Stephen R. Daley, Paul G. Thomas, Jamie Rossjohn

Research output: Contribution to journalReview ArticleResearchpeer-review

150 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)467-478
Number of pages12
JournalNature Reviews Immunology
Publication statusPublished - Jul 2018


  • antigen presentation
  • MHC
  • T-cell receptor

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