Codification of bidentate pMHC interaction with TCR and its co-receptor

Trends Immunol. 2015 May;36(5):300-6. doi: 10.1016/j.it.2015.03.004. Epub 2015 Mar 26.

Abstract

A 1983 Immunology Today rostrum hypothesized that each T cell has two recognition units: a T cell receptor (TCR) complex, which binds antigen associated with a polymorphic region of a MHC molecule (pMHC), and a CD4 or CD8 molecule that binds to a conserved region of that same MHC gene product (class II or I, respectively). Structural biology has since precisely revealed those bidentate pMHC interactions. TCRαβ ligates the membrane-distal antigen-binding MHC platform, whereas CD8 clamps a membrane-proximal MHCI α3 domain loop and CD4 docks to a hydrophobic crevice between MHCII α2 and β2 domains. Here, we review how MHC class-restricted binding impacts signaling and lineage commitment, discussing TCR force-driven conformational transitions that may optimally expose the co-receptor docking site on MHC.

Keywords: TCR; antigen recognition; co-receptor; mechanobiology.

Publication types

  • Review

MeSH terms

  • Animals
  • Histocompatibility Antigens / chemistry
  • Histocompatibility Antigens / immunology*
  • Histocompatibility Antigens / metabolism*
  • Humans
  • Major Histocompatibility Complex / physiology*
  • Models, Biological
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Protein Multimerization
  • Receptors, Antigen, T-Cell / chemistry
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Histocompatibility Antigens
  • Receptors, Antigen, T-Cell