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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F23%3A00567836" target="_blank" >RIV/68378050:_____/23:00567836 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/s41590-022-01366-0" target="_blank" >https://www.nature.com/articles/s41590-022-01366-0</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41590-022-01366-0" target="_blank" >10.1038/s41590-022-01366-0</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature Immunology

ISSN

1529-2908

e-ISSN

1529-2916

Svazek periodika

24

Číslo periodika v rámci svazku

23 Jan

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

33

Strana od-do

174-185

Kód UT WoS článku

000910247400001

EID výsledku v databázi Scopus

2-s2.0-85144706402