Open AccessCD8 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 Llewellyn-Lacey,
Anzelika Rubina,
Ore Francis,
D.K. Cole,
Andrew K. Sewell,
John S. Bridgeman,
David A. Price,
Hugo van den Berg,
Linda Wooldridge
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
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 , major histocompatibility complex , biology , agonist , peptide , receptor , antigen , cytotoxic t cell , mhc class i , t cell , microbiology and biotechnology , computational biology , immunology , biochemistry , in vitro , immune system
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.