Evidence that the density of self peptide-MHC ligands regulates T-cell receptor signaling.

Noncognate or self peptide-MHC (pMHC) ligands productively interact with T-cell receptor (TCR) and are always in a large access over the cognate pMHC on the surface of antigen presenting cells. We assembled soluble cognate and noncognate pMHC class I (pMHC-I) ligands at designated ratios on various...

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Main Authors: Nadia Anikeeva, Dimitry Gakamsky, Jørgen Schøller, Yuri Sykulev
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3411518?pdf=render
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author Nadia Anikeeva
Dimitry Gakamsky
Jørgen Schøller
Yuri Sykulev
author_facet Nadia Anikeeva
Dimitry Gakamsky
Jørgen Schøller
Yuri Sykulev
author_sort Nadia Anikeeva
collection DOAJ
description Noncognate or self peptide-MHC (pMHC) ligands productively interact with T-cell receptor (TCR) and are always in a large access over the cognate pMHC on the surface of antigen presenting cells. We assembled soluble cognate and noncognate pMHC class I (pMHC-I) ligands at designated ratios on various scaffolds into oligomers that mimic pMHC clustering and examined how multivalency and density of the pMHCs in model clusters influences the binding to live CD8 T cells and the kinetics of TCR signaling. Our data demonstrate that the density of self pMHC-I proteins promotes their interaction with CD8 co-receptor, which plays a critical role in recognition of a small number of cognate pMHC-I ligands. This suggests that MHC clustering on live target cells could be utilized as a sensitive mechanism to regulate T cell responsiveness.
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spelling doaj.art-a932f4b731ad4e4baaf0c975f629bf412022-12-21T23:50:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4146610.1371/journal.pone.0041466Evidence that the density of self peptide-MHC ligands regulates T-cell receptor signaling.Nadia AnikeevaDimitry GakamskyJørgen SchøllerYuri SykulevNoncognate or self peptide-MHC (pMHC) ligands productively interact with T-cell receptor (TCR) and are always in a large access over the cognate pMHC on the surface of antigen presenting cells. We assembled soluble cognate and noncognate pMHC class I (pMHC-I) ligands at designated ratios on various scaffolds into oligomers that mimic pMHC clustering and examined how multivalency and density of the pMHCs in model clusters influences the binding to live CD8 T cells and the kinetics of TCR signaling. Our data demonstrate that the density of self pMHC-I proteins promotes their interaction with CD8 co-receptor, which plays a critical role in recognition of a small number of cognate pMHC-I ligands. This suggests that MHC clustering on live target cells could be utilized as a sensitive mechanism to regulate T cell responsiveness.http://europepmc.org/articles/PMC3411518?pdf=render
spellingShingle Nadia Anikeeva
Dimitry Gakamsky
Jørgen Schøller
Yuri Sykulev
Evidence that the density of self peptide-MHC ligands regulates T-cell receptor signaling.
PLoS ONE
title Evidence that the density of self peptide-MHC ligands regulates T-cell receptor signaling.
title_full Evidence that the density of self peptide-MHC ligands regulates T-cell receptor signaling.
title_fullStr Evidence that the density of self peptide-MHC ligands regulates T-cell receptor signaling.
title_full_unstemmed Evidence that the density of self peptide-MHC ligands regulates T-cell receptor signaling.
title_short Evidence that the density of self peptide-MHC ligands regulates T-cell receptor signaling.
title_sort evidence that the density of self peptide mhc ligands regulates t cell receptor signaling
url http://europepmc.org/articles/PMC3411518?pdf=render
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AT jørgenschøller evidencethatthedensityofselfpeptidemhcligandsregulatestcellreceptorsignaling
AT yurisykulev evidencethatthedensityofselfpeptidemhcligandsregulatestcellreceptorsignaling