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

by Dockree, Tamsin , van den Berg, Hugo A. , Clement, Mathew , Rubina, Anzelika , Knezevic, Lea , McLaren, James E. , Miners, Kelly L. , Sewell, Andrew K. , Ladell, Kristin , Bridgeman, John S. , Francis, Ore , Cole, David K. , Wooldridge, Linda , Price, David A. , Llewellyn-Lacey, Sian

in Agonists / Antigens / Antigens - chemistry / Antigens - immunology / Biological effects / Biological Sciences / CD8 antigen / CD8 Antigens - immunology / CD8-Positive T-Lymphocytes - immunology / Cross Reactions / Histocompatibility Antigens Class I - genetics / Histocompatibility Antigens Class I - immunology / Humans / Immunology and Inflammation / Kinetics / Ligands / Lymphocyte Activation / Lymphocytes / Lymphocytes T / Major histocompatibility complex / Models, Immunological / Mutation / Peptides / Peptides - agonists / Peptides - immunology / Receptors / Receptors, Antigen, T-Cell - immunology / Sensitivity enhancement / T cell receptors

2021

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

2021

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

2021

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Journal Article

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

Dockree, Tamsin,

van den Berg, Hugo A.,

Clement, Mathew,

Rubina, Anzelika,

Knezevic, Lea,

McLaren, James E.,

Miners, Kelly L.,

Sewell, Andrew K.,

Ladell, Kristin,

Bridgeman, John S.,

Francis, Ore,

Cole, David K.,

Wooldridge, Linda,

Price, David A.,

Llewellyn-Lacey, Sian

2021

Overview

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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Publisher

National Academy of Sciences

Subject

Agonists

/ Antigens

/ Antigens - chemistry

/ Antigens - immunology

/ Biological effects

/ Biological Sciences

/ CD8 antigen