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

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

doi:https://dx.doi.org/10.1038/s41590-022-01366-0

Number of the records: 1

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

1.

SYSNO ASEP	0567836
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Unique roles of co-receptor-bound LCK in helper and cytotoxic T cells
Author(s)	Horková, Veronika (UMG-J)_ORCID Drobek, Aleš (UMG-J)_ORCID Paprčková, Darina (UMG-J)_{ORCID, RID} Niederlová, Veronika (UMG-J)_ORCID Prasai, Avishek (UMG-J) Uleri, Valeria (UMG-J)_ORCID Glatzová, Daniela (UMG-J) Kraller, M. (AT) Cesneková, Michaela (UMG-J) Janušová, Šárka (UMG-J)_ORCID Šályová, Eva (UMG-J)_ORCID Tsyklauri, Oksana (UMG-J) Kadlecek, T.A. (US) Křížová, Kateřina (UMG-J) Platzer, R. (AT) Schober, K. (DE) Busch, D. H. (DE) Weiss, A. (US) Huppa, J. B. (AT) Štěpánek, Ondřej (UMG-J)_{RID, ORCID}
Number of authors	20
Source Title	Nature Immunology. - : Nature Publishing Group - ISSN 1529-2908 Roč. 24, 23 Jan (2023), s. 174-185
Number of pages	33 s.
Language	eng - English
Country	US - United States
Keywords	tyrosine kinase ; positive selection ; self-reactivity ; cd4 ; coreceptor ; affinity ; binding ; mice ; involvement ; recognition
OECD category	Immunology
R&D Projects	LX22NPO5103 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	ED2.1.00/19.0395 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	EF16_013/0001789 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	LM2018129 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	EF18_046/0016045 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	EF16_013/0001775 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Method of publishing	Open access
Institutional support	UMG-J - RVO:68378050
UT WOS	000910247400001
EID SCOPUS	85144706402
DOI	10.1038/s41590-022-01366-0
Annotation	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.
Workplace	Institute of Molecular Genetics
Contact	Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217
Year of Publishing	2024
Electronic address	https://www.nature.com/articles/s41590-022-01366-0

Number of the records: 1