Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response

Antigen receptor diversity underpins adaptive immunity by providing the ground for clonal selection of lymphocytes with the appropriate antigen reactivity. Current models attribute T cell clonal selection during the immune response to T-cell receptor (TCR) affinity for either foreign or self peptide...

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Main Authors:	Merkenschlager, Julia, Ploquin, Mickaël J., Eksmond, Urszula, Andargachew, Rakieb, Thorborn, Georgina, Filby, Andrew, Pepper, Marion, Evavold, Brian, Kassiotis, George
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728444/

id	pubmed-4728444
recordtype	oai_dc
spelling	pubmed-47284442017-01-11 Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response Merkenschlager, Julia Ploquin, Mickaël J. Eksmond, Urszula Andargachew, Rakieb Thorborn, Georgina Filby, Andrew Pepper, Marion Evavold, Brian Kassiotis, George Article Antigen receptor diversity underpins adaptive immunity by providing the ground for clonal selection of lymphocytes with the appropriate antigen reactivity. Current models attribute T cell clonal selection during the immune response to T-cell receptor (TCR) affinity for either foreign or self peptides. Here, we report that clonal selection of CD4+ T cells is also extrinsically regulated by B cells. In response to viral infection, the antigen-specific TCR repertoire is progressively diversified by staggered clonotypic expansion, according to functional avidity, which correlates with self-reactivity. Clonal expansion of lower-avidity T-cell clonotypes depends on availability of MHC II-expressing B cells, in turn influenced by B-cell activation. B cells clonotypically diversify the CD4+ T-cell response also to vaccination or tumour challenge, revealing a common effect. Nature Publishing Group 2016-01-05 /pmc/articles/PMC4728444/ /pubmed/26728651 http://dx.doi.org/10.1038/ncomms10281 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Merkenschlager, Julia Ploquin, Mickaël J. Eksmond, Urszula Andargachew, Rakieb Thorborn, Georgina Filby, Andrew Pepper, Marion Evavold, Brian Kassiotis, George
spellingShingle	Merkenschlager, Julia Ploquin, Mickaël J. Eksmond, Urszula Andargachew, Rakieb Thorborn, Georgina Filby, Andrew Pepper, Marion Evavold, Brian Kassiotis, George Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response
author_facet	Merkenschlager, Julia Ploquin, Mickaël J. Eksmond, Urszula Andargachew, Rakieb Thorborn, Georgina Filby, Andrew Pepper, Marion Evavold, Brian Kassiotis, George
author_sort	Merkenschlager, Julia
title	Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response
title_short	Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response
title_full	Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response
title_fullStr	Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response
title_full_unstemmed	Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response
title_sort	stepwise b-cell-dependent expansion of t helper clonotypes diversifies the t-cell response
description	Antigen receptor diversity underpins adaptive immunity by providing the ground for clonal selection of lymphocytes with the appropriate antigen reactivity. Current models attribute T cell clonal selection during the immune response to T-cell receptor (TCR) affinity for either foreign or self peptides. Here, we report that clonal selection of CD4+ T cells is also extrinsically regulated by B cells. In response to viral infection, the antigen-specific TCR repertoire is progressively diversified by staggered clonotypic expansion, according to functional avidity, which correlates with self-reactivity. Clonal expansion of lower-avidity T-cell clonotypes depends on availability of MHC II-expressing B cells, in turn influenced by B-cell activation. B cells clonotypically diversify the CD4+ T-cell response also to vaccination or tumour challenge, revealing a common effect.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728444/
_version_	1613528994020327424

Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response

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