Probing the effector and suppressive functions of human T cell subsets using antigen-specific engineered T cell receptors.

Activation of T cells through the engagement of the T cell receptors (TCRs) with specific peptide-MHC complexes on antigen presenting cells (APCs) is the major determinant for their proliferation, differentiation and display of effector functions. To assess the role of quantity and quality of peptid...

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Autores principales:	Qi Wan, Lina Kozhaya, Keren Imberg, Frances Mercer, Shi Zhong, Michelle Krogsgaard, Derya Unutmaz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b23f7f5023444eb2a4eb7065231ba18b
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spelling	oai:doaj.org-article:b23f7f5023444eb2a4eb7065231ba18b2021-11-18T07:56:56ZProbing the effector and suppressive functions of human T cell subsets using antigen-specific engineered T cell receptors.1932-620310.1371/journal.pone.0056302https://doaj.org/article/b23f7f5023444eb2a4eb7065231ba18b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23437112/?tool=EBIhttps://doaj.org/toc/1932-6203Activation of T cells through the engagement of the T cell receptors (TCRs) with specific peptide-MHC complexes on antigen presenting cells (APCs) is the major determinant for their proliferation, differentiation and display of effector functions. To assess the role of quantity and quality of peptide-MHC presentation in eliciting T cell activation and suppression functions, we genetically engineered human T cells with two TCRs that recognize HLA-A*0201-restricted peptides derived from either HIV or melanoma antigens. The engineered-TCRs are highly functional in both CD8(+) and CD4(+) T cells as assessed by the upregulation of activation markers, induction of cytokine secretion and cytotoxicity. We further demonstrated that engineered-TCRs can also be expressed on naïve human T cells, which are stimulated through APCs presenting specific peptides to induce T cell proliferation and acquire effector functions. Furthermore, regulatory T cells (Tregs) ectopically expressing the engineered-TCRs are activated in an antigen-specific fashion and suppress T cell proliferation. In this system, the inhibitory activity of peptide-stimulated Tregs require the presence of dendritic cells (DCs) in the culture, either as presenters or as bystander cells, pointing to a critical role for DCs in suppression by Tregs. In conclusion, the engineered-TCR system reported here advances our ability to understand the differentiation pathways of naïve T cells into antigen-specific effector cells and the role of antigen-specific signaling in Treg-mediated immune suppression.Qi WanLina KozhayaKeren ImbergFrances MercerShi ZhongMichelle KrogsgaardDerya UnutmazPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e56302 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qi Wan Lina Kozhaya Keren Imberg Frances Mercer Shi Zhong Michelle Krogsgaard Derya Unutmaz Probing the effector and suppressive functions of human T cell subsets using antigen-specific engineered T cell receptors.
description	Activation of T cells through the engagement of the T cell receptors (TCRs) with specific peptide-MHC complexes on antigen presenting cells (APCs) is the major determinant for their proliferation, differentiation and display of effector functions. To assess the role of quantity and quality of peptide-MHC presentation in eliciting T cell activation and suppression functions, we genetically engineered human T cells with two TCRs that recognize HLA-A*0201-restricted peptides derived from either HIV or melanoma antigens. The engineered-TCRs are highly functional in both CD8(+) and CD4(+) T cells as assessed by the upregulation of activation markers, induction of cytokine secretion and cytotoxicity. We further demonstrated that engineered-TCRs can also be expressed on naïve human T cells, which are stimulated through APCs presenting specific peptides to induce T cell proliferation and acquire effector functions. Furthermore, regulatory T cells (Tregs) ectopically expressing the engineered-TCRs are activated in an antigen-specific fashion and suppress T cell proliferation. In this system, the inhibitory activity of peptide-stimulated Tregs require the presence of dendritic cells (DCs) in the culture, either as presenters or as bystander cells, pointing to a critical role for DCs in suppression by Tregs. In conclusion, the engineered-TCR system reported here advances our ability to understand the differentiation pathways of naïve T cells into antigen-specific effector cells and the role of antigen-specific signaling in Treg-mediated immune suppression.
format	article
author	Qi Wan Lina Kozhaya Keren Imberg Frances Mercer Shi Zhong Michelle Krogsgaard Derya Unutmaz
author_facet	Qi Wan Lina Kozhaya Keren Imberg Frances Mercer Shi Zhong Michelle Krogsgaard Derya Unutmaz
author_sort	Qi Wan
title	Probing the effector and suppressive functions of human T cell subsets using antigen-specific engineered T cell receptors.
title_short	Probing the effector and suppressive functions of human T cell subsets using antigen-specific engineered T cell receptors.
title_full	Probing the effector and suppressive functions of human T cell subsets using antigen-specific engineered T cell receptors.
title_fullStr	Probing the effector and suppressive functions of human T cell subsets using antigen-specific engineered T cell receptors.
title_full_unstemmed	Probing the effector and suppressive functions of human T cell subsets using antigen-specific engineered T cell receptors.
title_sort	probing the effector and suppressive functions of human t cell subsets using antigen-specific engineered t cell receptors.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/b23f7f5023444eb2a4eb7065231ba18b
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Probing the effector and suppressive functions of human T cell subsets using antigen-specific engineered T cell receptors.

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