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Title: TCR affinity biases Th cell differentiation by regulating CD25, Eef1e1, and Gbp2
Authors: Kotov, Dmitri I.
Mitchell, Jason S.
Pengo, Thomas
Ruedl, Christiane
Way, Sing Sing
Langlois, Ryan A.
Fife, Brian T.
Jenkins, Marc K.
Keywords: DRNTU::Science::Biological sciences
TCR Affinity
Th Cell
Issue Date: 2019
Source: 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
Series/Report no.: The Journal of Immunology
Abstract: 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.
ISSN: 0022-1767
DOI: 10.4049/jimmunol.1801609
Rights: © 2019 The American Association of Immunologists, Inc. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
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