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| Item Type: | Article |
|---|---|
| Title: | Unique roles of co-receptor-bound LCK in helper and cytotoxic T cells |
| Creators Name: | Horkova, V., Drobek, A., Paprckova, D., Niederlova, V., Prasai, A., Uleri, V., Glatzova, D., Kraller, M., Cesnekova, M., Janusova, S., Salyova, E., Tsyklauri, O., Kadlecek, T.A., Krizova, K., Platzer, R., Schober, K., Busch, D.H., Weiss, A., Huppa, J.B. and Stepanek, O. |
| Abstract: | 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. |
| Keywords: | CD4 Antigens, CD8 Antigens, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), T-Cell Antigen Receptors, Signal Transduction, Cytotoxic T-Lymphocytes, Animals, Mice |
| Source: | Nature Immunology |
| ISSN: | 1529-2908 |
| Publisher: | Nature Publishing Group |
| Volume: | 24 |
| Number: | 1 |
| Page Range: | 174-185 |
| Date: | January 2023 |
| Official Publication: | https://doi.org/10.1038/s41590-022-01366-0 |
| PubMed: | View item in PubMed |
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