THE ROLE OF LCK IN THE FORMATION OFEFFECTOR AND MEMORY T CELLS

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F23%3A00580717" target="_blank" >RIV/68378050:_____/23:00580717 - isvavai.cz</a>

Výsledek na webu

<a href="http://ccsss.cz/index.php/ccsss/issue/view/41" target="_blank" >http://ccsss.cz/index.php/ccsss/issue/view/41</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

THE ROLE OF LCK IN THE FORMATION OFEFFECTOR AND MEMORY T CELLS

Popis výsledku v původním jazyce

T cells play a critical role in the immune response, defending the host against a wide range of pathogens, viruses, cancer, and allergies.To ensure protection, T cells use their unique T cell receptor (TCR) in combination with co-receptors to recognize their cognate antigen presented on the antigen-presenting cells1. Upon antigen recognition, T cells trigger a signaling cascade that turns into transcriptional changes and T cell activation.The first biochemical event after the antigen recognition is the phosphorylation of the immunoreceptor tyrosine-based activation motifs in the CD3 chains by Src-family kinases (SFK), primarily by LCK and, to a lesser extent, by FYN2. Previous studies demonstrated the importance of LCK in T cell development, still its role in periphery is not fully understood. Therefore, the main aim of this study is to define the role of LCK and co-receptors in T cell signaling in peripheral T cells and investigate their importance in T cell differentiation into effector or memory T cells. Ourpreliminary results, obtained using CD8+ T cells isolated from LCK KO and LCK WT OT-I mice and adoptively transferred into congenic Ly5.1 hosts, show that LCK KO OT-I cells are able to expand despite producing weaker immune responses than their WT counterparts. We expected that LCK KO OT-I cells would receive a lower activation signaling and, therefore, resemble the immunological response produced after the encounter of T cells with a low affinity antigen. Instead, FACS analysis conducted 6 and 30 days after infection showed that LCK KO OT-I form more KLRG1+ CD127-cells in comparison to WT. These results suggest that the recruitment of the LCK to the immunological synapse might be important in ensuring proper cell polarization during division. Consequently, we believe that LCK KO T cells might be committed toward the effector lineage rather than memory. This study will contribute to a better understanding of T cell biology and could have potentially important implications for the development of novel immunotherapies

Název v anglickém jazyce

THE ROLE OF LCK IN THE FORMATION OFEFFECTOR AND MEMORY T CELLS

Popis výsledku anglicky

T cells play a critical role in the immune response, defending the host against a wide range of pathogens, viruses, cancer, and allergies.To ensure protection, T cells use their unique T cell receptor (TCR) in combination with co-receptors to recognize their cognate antigen presented on the antigen-presenting cells1. Upon antigen recognition, T cells trigger a signaling cascade that turns into transcriptional changes and T cell activation.The first biochemical event after the antigen recognition is the phosphorylation of the immunoreceptor tyrosine-based activation motifs in the CD3 chains by Src-family kinases (SFK), primarily by LCK and, to a lesser extent, by FYN2. Previous studies demonstrated the importance of LCK in T cell development, still its role in periphery is not fully understood. Therefore, the main aim of this study is to define the role of LCK and co-receptors in T cell signaling in peripheral T cells and investigate their importance in T cell differentiation into effector or memory T cells. Ourpreliminary results, obtained using CD8+ T cells isolated from LCK KO and LCK WT OT-I mice and adoptively transferred into congenic Ly5.1 hosts, show that LCK KO OT-I cells are able to expand despite producing weaker immune responses than their WT counterparts. We expected that LCK KO OT-I cells would receive a lower activation signaling and, therefore, resemble the immunological response produced after the encounter of T cells with a low affinity antigen. Instead, FACS analysis conducted 6 and 30 days after infection showed that LCK KO OT-I form more KLRG1+ CD127-cells in comparison to WT. These results suggest that the recruitment of the LCK to the immunological synapse might be important in ensuring proper cell polarization during division. Consequently, we believe that LCK KO T cells might be committed toward the effector lineage rather than memory. This study will contribute to a better understanding of T cell biology and could have potentially important implications for the development of novel immunotherapies

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30102 - Immunology

Projekt

<a href="/cs/project/LX22NPO5103" target="_blank" >LX22NPO5103: Národní institut virologie a bakteriologie</a><br>

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