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CD8 coreceptor-mediated focusing can reorder the agonist hierarchy of peptide ligands recognized via the T cell

Mathew Clement1, Lea Knezevic2, Tamsin Dockree1

  • 1Division of Infection and Immunity, Cardiff University School of Medicine, University Hospital of Wales, Cardiff CF14 4XN, United Kingdom.

Proceedings of the National Academy of Sciences of the United States of America
|July 17, 2021
PubMed

CD8+ T cells are inherently cross-reactive and recognize numerous peptide antigens in the context of a given major histocompatibility complex class I (MHCI) molecule via the clonotypically expressed T cell receptor (TCR). The lineally expressed coreceptor CD8 interacts coordinately with MHCI at a distinct and largely invariant site to slow the TCR/peptide-MHCI (pMHCI) dissociation rate and enhance antigen sensitivity. However, this biological effect is not necessarily uniform, and theoretical models suggest that antigen sensitivity can be modulated in a differential manner by CD8. We used two intrinsically controlled systems to determine how the relationship between the TCR/pMHCI interaction and the pMHCI/CD8 interaction affects the functional sensitivity of antigen recognition. Our data show that modulation of the pMHCI/CD8 interaction can reorder the agonist hierarchy of peptide ligands across a spectrum of affinities for the TCR.

Keywords:
CD8 coreceptorT cell activationpMHCI

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