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Increased Synapse Formation Obtained by T Cell Epitopes Containing a CxxC Motif in Flanking Residues Convert CD4+ T Cells into Cytolytic Effectors

The nature of MHC class II-binding epitopes not only determines the specificity of T cell responses, but may also alter effector cell functions. Cytolytic CD4+ T cells have been observed primarily in anti-viral responses, but very little is known about the conditions under which they can be elicited...

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Autores principales: Carlier, Vincent A., VanderElst, Luc, Janssens, Wim, Jacquemin, Marc G., Saint-Remy, Jean-Marie R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3467281/
https://www.ncbi.nlm.nih.gov/pubmed/23056200
http://dx.doi.org/10.1371/journal.pone.0045366
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author Carlier, Vincent A.
VanderElst, Luc
Janssens, Wim
Jacquemin, Marc G.
Saint-Remy, Jean-Marie R.
author_facet Carlier, Vincent A.
VanderElst, Luc
Janssens, Wim
Jacquemin, Marc G.
Saint-Remy, Jean-Marie R.
author_sort Carlier, Vincent A.
collection PubMed
description The nature of MHC class II-binding epitopes not only determines the specificity of T cell responses, but may also alter effector cell functions. Cytolytic CD4+ T cells have been observed primarily in anti-viral responses, but very little is known about the conditions under which they can be elicited. Their potential as regulators of immune responses, however, deserves investigations. We describe here that inclusion of a thiol-disulfide oxidoreductase motif within flanking residues of class II-restricted epitopes results, both in vitro and in vivo, in elicitation of antigen-specific cytolytic CD4+ T cells through increased synapse formation. We show that both naïve and polarized CD4+ T cells, including Th17 cells, can be converted by cognate recognition of such modified epitopes. Cytolytic CD4+ T cells induce apoptosis on APCs by Fas-FasL interaction. These findings potentially open the way towards a novel form of antigen-specific immunosuppression.
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spelling pubmed-34672812012-10-10 Increased Synapse Formation Obtained by T Cell Epitopes Containing a CxxC Motif in Flanking Residues Convert CD4+ T Cells into Cytolytic Effectors Carlier, Vincent A. VanderElst, Luc Janssens, Wim Jacquemin, Marc G. Saint-Remy, Jean-Marie R. PLoS One Research Article The nature of MHC class II-binding epitopes not only determines the specificity of T cell responses, but may also alter effector cell functions. Cytolytic CD4+ T cells have been observed primarily in anti-viral responses, but very little is known about the conditions under which they can be elicited. Their potential as regulators of immune responses, however, deserves investigations. We describe here that inclusion of a thiol-disulfide oxidoreductase motif within flanking residues of class II-restricted epitopes results, both in vitro and in vivo, in elicitation of antigen-specific cytolytic CD4+ T cells through increased synapse formation. We show that both naïve and polarized CD4+ T cells, including Th17 cells, can be converted by cognate recognition of such modified epitopes. Cytolytic CD4+ T cells induce apoptosis on APCs by Fas-FasL interaction. These findings potentially open the way towards a novel form of antigen-specific immunosuppression. Public Library of Science 2012-10-09 /pmc/articles/PMC3467281/ /pubmed/23056200 http://dx.doi.org/10.1371/journal.pone.0045366 Text en © 2012 Carlier et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Carlier, Vincent A.
VanderElst, Luc
Janssens, Wim
Jacquemin, Marc G.
Saint-Remy, Jean-Marie R.
Increased Synapse Formation Obtained by T Cell Epitopes Containing a CxxC Motif in Flanking Residues Convert CD4+ T Cells into Cytolytic Effectors
title Increased Synapse Formation Obtained by T Cell Epitopes Containing a CxxC Motif in Flanking Residues Convert CD4+ T Cells into Cytolytic Effectors
title_full Increased Synapse Formation Obtained by T Cell Epitopes Containing a CxxC Motif in Flanking Residues Convert CD4+ T Cells into Cytolytic Effectors
title_fullStr Increased Synapse Formation Obtained by T Cell Epitopes Containing a CxxC Motif in Flanking Residues Convert CD4+ T Cells into Cytolytic Effectors
title_full_unstemmed Increased Synapse Formation Obtained by T Cell Epitopes Containing a CxxC Motif in Flanking Residues Convert CD4+ T Cells into Cytolytic Effectors
title_short Increased Synapse Formation Obtained by T Cell Epitopes Containing a CxxC Motif in Flanking Residues Convert CD4+ T Cells into Cytolytic Effectors
title_sort increased synapse formation obtained by t cell epitopes containing a cxxc motif in flanking residues convert cd4+ t cells into cytolytic effectors
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3467281/
https://www.ncbi.nlm.nih.gov/pubmed/23056200
http://dx.doi.org/10.1371/journal.pone.0045366
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