TCR affinity biases Th cell differentiation by regulating CD25, Eef1e1, and Gbp2

Naive CD4+ T lymphocytes differentiate into various Th cell subsets following TCR binding to microbial peptide:MHC class II (p:MHCII) complexes on dendritic cells (DCs). The affinity of the TCR interaction with p:MHCII plays a role in Th differentiation by mechanisms that are not completely understo...

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Main Authors: Kotov, Dmitri I., Mitchell, Jason S., Pengo, Thomas, Ruedl, Christiane, Way, Sing Sing, Langlois, Ryan A., Fife, Brian T., Jenkins, Marc K.
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2019
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Online Access:https://hdl.handle.net/10356/105928
http://hdl.handle.net/10220/48821
http://dx.doi.org/10.4049/jimmunol.1801609
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1059282019-12-06T22:00:52Z TCR affinity biases Th cell differentiation by regulating CD25, Eef1e1, and Gbp2 Kotov, Dmitri I. Mitchell, Jason S. Pengo, Thomas Ruedl, Christiane Way, Sing Sing Langlois, Ryan A. Fife, Brian T. Jenkins, Marc K. School of Biological Sciences DRNTU::Science::Biological sciences TCR Affinity Th Cell Naive CD4+ T lymphocytes differentiate into various Th cell subsets following TCR binding to microbial peptide:MHC class II (p:MHCII) complexes on dendritic cells (DCs). The affinity of the TCR interaction with p:MHCII plays a role in Th differentiation by mechanisms that are not completely understood. We found that low-affinity TCRs biased mouse naive T cells to become T follicular helper (Tfh) cells, whereas higher-affinity TCRs promoted the formation of Th1 or Th17 cells. We explored the basis for this phenomenon by focusing on IL-2R signaling, which is known to promote Th1 and suppress Tfh cell differentiation. SIRP⍺+ DCs produce abundant p:MHCII complexes and consume IL-2, whereas XCR1+ DCs weakly produce p:MHCII but do not consume IL-2. We found no evidence, however, of preferential interactions between Th1 cell–prone, high-affinity T cells and XCR1+ DCs or Tfh cell–prone, low-affinity T cells and SIRP⍺+ DCs postinfection with bacteria expressing the peptide of interest. Rather, high-affinity T cells sustained IL-2R expression longer and expressed two novel Th cell differentiation regulators, Eef1e1 and Gbp2, to a higher level than low-affinity T cells. These results suggest that TCR affinity does not influence Th cell differentiation by biasing T cell interactions with IL-2–consuming DCs, but instead, directly regulates genes in naive T cells that control the differentiation process. 2019-06-19T03:18:45Z 2019-12-06T22:00:52Z 2019-06-19T03:18:45Z 2019-12-06T22:00:52Z 2019 Journal Article Kotov, D. I., Mitchell, J. S., Pengo, T., Ruedl, C., Way, S. S., Langlois, R. A., . . . Jenkins, M. K. (2019). TCR affinity biases Th cell differentiation by regulating CD25, Eef1e1, and Gbp2. The Journal of Immunology, 202(9), 2535-2545. doi:10.4049/jimmunol.1801609 0022-1767 https://hdl.handle.net/10356/105928 http://hdl.handle.net/10220/48821 http://dx.doi.org/10.4049/jimmunol.1801609 en The Journal of Immunology © 2019 The American Association of Immunologists, Inc. All rights reserved.
institution Nanyang Technological University
building NTU Library
country Singapore
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
TCR Affinity
Th Cell
spellingShingle DRNTU::Science::Biological sciences
TCR Affinity
Th Cell
Kotov, Dmitri I.
Mitchell, Jason S.
Pengo, Thomas
Ruedl, Christiane
Way, Sing Sing
Langlois, Ryan A.
Fife, Brian T.
Jenkins, Marc K.
TCR affinity biases Th cell differentiation by regulating CD25, Eef1e1, and Gbp2
description Naive CD4+ T lymphocytes differentiate into various Th cell subsets following TCR binding to microbial peptide:MHC class II (p:MHCII) complexes on dendritic cells (DCs). The affinity of the TCR interaction with p:MHCII plays a role in Th differentiation by mechanisms that are not completely understood. We found that low-affinity TCRs biased mouse naive T cells to become T follicular helper (Tfh) cells, whereas higher-affinity TCRs promoted the formation of Th1 or Th17 cells. We explored the basis for this phenomenon by focusing on IL-2R signaling, which is known to promote Th1 and suppress Tfh cell differentiation. SIRP⍺+ DCs produce abundant p:MHCII complexes and consume IL-2, whereas XCR1+ DCs weakly produce p:MHCII but do not consume IL-2. We found no evidence, however, of preferential interactions between Th1 cell–prone, high-affinity T cells and XCR1+ DCs or Tfh cell–prone, low-affinity T cells and SIRP⍺+ DCs postinfection with bacteria expressing the peptide of interest. Rather, high-affinity T cells sustained IL-2R expression longer and expressed two novel Th cell differentiation regulators, Eef1e1 and Gbp2, to a higher level than low-affinity T cells. These results suggest that TCR affinity does not influence Th cell differentiation by biasing T cell interactions with IL-2–consuming DCs, but instead, directly regulates genes in naive T cells that control the differentiation process.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Kotov, Dmitri I.
Mitchell, Jason S.
Pengo, Thomas
Ruedl, Christiane
Way, Sing Sing
Langlois, Ryan A.
Fife, Brian T.
Jenkins, Marc K.
format Article
author Kotov, Dmitri I.
Mitchell, Jason S.
Pengo, Thomas
Ruedl, Christiane
Way, Sing Sing
Langlois, Ryan A.
Fife, Brian T.
Jenkins, Marc K.
author_sort Kotov, Dmitri I.
title TCR affinity biases Th cell differentiation by regulating CD25, Eef1e1, and Gbp2
title_short TCR affinity biases Th cell differentiation by regulating CD25, Eef1e1, and Gbp2
title_full TCR affinity biases Th cell differentiation by regulating CD25, Eef1e1, and Gbp2
title_fullStr TCR affinity biases Th cell differentiation by regulating CD25, Eef1e1, and Gbp2
title_full_unstemmed TCR affinity biases Th cell differentiation by regulating CD25, Eef1e1, and Gbp2
title_sort tcr affinity biases th cell differentiation by regulating cd25, eef1e1, and gbp2
publishDate 2019
url https://hdl.handle.net/10356/105928
http://hdl.handle.net/10220/48821
http://dx.doi.org/10.4049/jimmunol.1801609
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