| First Author | Kotov DI | Year | 2019 |
| Journal | J Immunol | Volume | 202 |
| Issue | 9 | Pages | 2535-2545 |
| PubMed ID | 30858199 | Mgi Jnum | J:274587 |
| Mgi Id | MGI:6296927 | Doi | 10.4049/jimmunol.1801609 |
| Citation | Kotov DI, et al. (2019) TCR Affinity Biases Th Cell Differentiation by Regulating CD25, Eef1e1, and Gbp2. J Immunol 202(9):2535-2545 |
| abstractText | 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. |
