| First Author | Horkova V | Year | 2023 |
| Journal | Nat Immunol | Volume | 24 |
| Issue | 1 | Pages | 174-185 |
| PubMed ID | 36564464 | Mgi Jnum | J:337691 |
| Mgi Id | MGI:7495964 | Doi | 10.1038/s41590-022-01366-0 |
| Citation | Horkova V, et al. (2023) Unique roles of co-receptor-bound LCK in helper and cytotoxic T cells. Nat Immunol 24(1):174-185 |
| abstractText | The kinase LCK and CD4/CD8 co-receptors are crucial components of the T cell antigen receptor (TCR) signaling machinery, leading to key T cell fate decisions. Despite decades of research, the roles of CD4-LCK and CD8-LCK interactions in TCR triggering in vivo remain unknown. In this study, we created animal models expressing endogenous levels of modified LCK to resolve whether and how co-receptor-bound LCK drives TCR signaling. We demonstrated that the role of LCK depends on the co-receptor to which it is bound. The CD8-bound LCK is largely dispensable for antiviral and antitumor activity of cytotoxic T cells in mice; however, it facilitates CD8(+) T cell responses to suboptimal antigens in a kinase-dependent manner. By contrast, the CD4-bound LCK is required for efficient development and function of helper T cells via a kinase-independent stabilization of surface CD4. Overall, our findings reveal the role of co-receptor-bound LCK in T cell biology, show that CD4- and CD8-bound LCK drive T cell development and effector immune responses using qualitatively different mechanisms and identify the co-receptor-LCK interactions as promising targets for immunomodulation. |
