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

• Autores: Ellis L. Reinherz, Jia Huai Wang
• Localización: Trends in immunology, ISSN 1471-4906, Vol. 36, Nº. 5, 2015, págs. 300-306
• Idioma: inglés
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• Resumen

  • 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.