| First Author | Wither MJ | Year | 2023 |
| Journal | bioRxiv | PubMed ID | 37333368 |
| Mgi Jnum | J:342890 | Mgi Id | MGI:7562148 |
| Doi | 10.1101/2023.06.01.543260 | Citation | Wither MJ, Whilte WL, Pendyala S, Leanza PJ, Fowler D, Kueh HY (2023) Antigen perception in T cells by long-term Erk and NFAT signaling dynamics. bioRxiv |
| abstractText | Immune system threat detection hinges on T cellsâ ability to perceive varying peptide major-histocompatibility complex (pMHC) antigens. As the Erk and NFAT pathways link T cell receptor engagement to gene regulation, their signaling dynamics may convey information about pMHC inputs. To test this idea, we developed a dual reporter mouse strain and a quantitative imaging assay that, together, enable simultaneous monitoring of Erk and NFAT dynamics in live T cells over day-long timescales as they respond to varying pMHC inputs. Both pathways initially activate uniformly across various pMHC inputs, but diverge only over longer (9+ hrs) timescales, enabling independent encoding of pMHC affinity and dose. These late signaling dynamics are decoded via multiple temporal and combinatorial mechanisms to generate pMHC-specific transcriptional responses. Our findings underscore the importance of long timescale signaling dynamics in antigen perception, and establish a framework for understanding T cell responses under diverse contexts. |
