Requirement for AHNAK1 -mediated calcium signaling during T lymphocyte cytolysis

摘要

Cytolytic CD8~+ T cells (CTLs) kill virally infected cells, tumor cells, or other potentially autoreactive T cells in a calcium-dependent manner. To date, the molecular mechanism that leads to calcium intake during CTL differentiation and function has remained unresolved. We demonstrate that desmoyokin (AHNAK1) is expressed in mature CTLs, but not in naive CD8~+ T cells, and is critical for calcium entry required for their proper function during immune response. We show that mature AHNAK1-deficient CTLs exhibit reduced Ca_v1.1 α1 subunit expression (also referred to as L-type calcium channels or a1S pore-forming subunits), which recently were suggested to play a role in calcium entry into CD4~+ T cells. AHNAK1-deficient CTLs show marked reduction in granzyme-B production, cytolytic activity, and IFN-γ secretion after T cell receptor stimulation. Our results demonstrate an AHNAK1-depen-dent mechanism controlling calcium entry during CTL effector function.