Srovnání aktivity kináz LCK a FYN v T-buněčné antigenní signalizaci

Ráček, Vojtěch

T-cell receptor (TCR) signaling is primarily driven by the SRC-family kinase lymphocyte-specific kinase (LCK). Another member of this family, the FYN kinase, is known to share partially overlapping functions with LCK. However, the extent of functional redundancy between these kinases remains unclear. To address this, we combined in vitro analyses using Jurkat T cell lines with in vivo studies in genetically modified mouse models. In Jurkat LCK knockout cells, only constitutively active, but not wild-type, FYN provided a partial rescue of TCR signaling. In primary mouse T cells, we examined the dynamic expression of these kinases during thymic development, identifying kinase abundance as an additional layer of TCR signal tuning. In vivo, LCK-deficient CD8⁺ T cells remained capable of responding to infection, but exhibited impaired clonal expansion together with a pronounced bias toward effector differentiation. This phenotype was observed across both acute and inducible models of LCK deletion. Together, our findings demonstrate that LCK is not strictly required for initiation of TCR signaling but is essential for linking activation to proliferation and shaping differentiation. In contrast, FYN provides limited compensatory capacity, and its signaling in the absence of LCK is biased toward effector...

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