| First Author | Wither MJ | Year | 2023 |
| Journal | Proc Natl Acad Sci U S A | Volume | 120 |
| Issue | 52 | Pages | e2308366120 |
| PubMed ID | 38113261 | Mgi Jnum | J:349935 |
| Mgi Id | MGI:7660503 | Doi | 10.1073/pnas.2308366120 |
| Citation | Wither MJ, et al. (2023) Antigen perception in T cells by long-term Erk and NFAT signaling dynamics. Proc Natl Acad Sci U S A 120(52):e2308366120 |
| abstractText | Immune system threat detection hinges on T cells' 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+ h) 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. |
