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

Mathew Clement | Zendy; Lea Knežević | Zendy; Tamsin Dockree | Zendy; James E. McLaren | Zendy; Kristin Ladell | Zendy; Kelly L. Miners | Zendy; Sian LlewellynLacey | Zendy; Anzelika Rubina | Zendy; Ore Francis | Zendy; David K. Cole | Zendy; Andrew K. Sewell | Zendy; John S. Bridgeman | Zendy; David A. Price | Zendy; Hugo A. van den Berg | Zendy; Linda Wooldridge | Zendy

Open Access

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

Author(s) -

Mathew Clement,

Lea Knežević,

Tamsin Dockree,

James E. McLaren,

Kristin Ladell,

Kelly L. Miners,

Sian LlewellynLacey,

Anzelika Rubina,

Ore Francis,

David K. Cole,

Andrew K. Sewell,

John S. Bridgeman,

David A. Price,

Hugo A. van den Berg,

Linda Wooldridge

Publication year - 2021

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.2019639118

Subject(s) - t cell receptor , cd8 , receptor , autoimmunity , computational biology , agonist , t cell , peptide , cytotoxic t cell , immune system , microbiology and biotechnology , biology , chemistry , immunology , genetics , biochemistry , in vitro

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.

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