Open AccessRequirement for AHNAK1-mediated calcium signaling during T lymphocyte cytolysis
Author(s) -
Didi Matza,
Abdallah Badou,
Mithilesh Kumar Jha,
Tim Willinger,
Andrey Antov,
Shomyseh Sanjabi,
Koichi S. Kobayashi,
V. Marchesi,
Richard A. Flavell
Publication year - 2009
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0902844106
Subject(s) - cytolysis , microbiology and biotechnology , cytotoxic t cell , biology , granzyme b , calcium , ctl* , cd8 , granzyme , immune system , perforin , immunology , chemistry , biochemistry , in vitro , organic chemistry
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 Cav 1.1 α1 subunit expression (also referred to as L-type calcium channels or α1S 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-dependent mechanism controlling calcium entry during CTL effector function.