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...
Saved in:
Main Authors: | , , , , , , , |
---|---|
Other Authors: | |
Format: | Article |
Language: | English |
Published: |
2019
|
Subjects: | |
Online Access: | https://hdl.handle.net/10356/105928 http://hdl.handle.net/10220/48821 http://dx.doi.org/10.4049/jimmunol.1801609 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Nanyang Technological University |
Language: | English |
id |
sg-ntu-dr.10356-105928 |
---|---|
record_format |
dspace |
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 |
_version_ |
1681049889002225664 |