Unique roles of co-receptor-bound LCK in helper and cytotoxic T cells

0567836 - ÚMG 2024 RIV US eng J - Článek v odborném periodiku
Horková, Veronika - Drobek, Aleš - Paprčková, Darina - Niederlová, Veronika - Prasai, Avishek - Uleri, Valeria - Glatzová, Daniela - Kraller, M. - Cesneková, Michaela - Janušová, Šárka - Šályová, Eva - Tsyklauri, Oksana - Kadlecek, T.A. - Křížová, Kateřina - Platzer, R. - Schober, K. - Busch, D. H. - Weiss, A. - Huppa, J. B. - Štěpánek, Ondřej
Unique roles of co-receptor-bound LCK in helper and cytotoxic T cells.
Nature Immunology. Roč. 24, 23 Jan (2023), s. 174-185. ISSN 1529-2908. E-ISSN 1529-2916
Grant CEP: GA MŠMT(CZ) LX22NPO5103; GA MŠMT ED2.1.00/19.0395; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT EF16_013/0001789; GA MŠMT(CZ) LM2018129; GA MŠMT(CZ) EF18_046/0016045; GA MŠMT(CZ) EF16_013/0001775
GRANT EU: European Commission(XE) 802878 - FunDiT
Institucionální podpora: RVO:68378050
Klíčová slova: tyrosine kinase * positive selection * self-reactivity * cd4 * coreceptor * affinity * binding * mice * involvement * recognition
Obor OECD: Immunology
Impakt faktor: 30.5, rok: 2022
Způsob publikování: Open access
https://www.nature.com/articles/s41590-022-01366-0

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.
Trvalý link: https://hdl.handle.net/11104/0339095