Loss of ARPC1B impairs cytotoxic T lymphocyte maintenance and cytolytic activity.

• DOI: 10.17863/cam.46931
• Publication Date: 2019-12-01
• Authors: Lyra O. Randzavola; Katharina Strege; Marie Juzans; Yukako Asano; Jane C. Stinchcombe; Christian M. Gawd...; Matthew Seaman; Taco W. Kuijpers; Gillian M. Griffiths
• Keywords: Immunological synapse; CTL*

CD8 cytotoxic T lymphocytes (CTLs) rely on rapid reorganization of the branched F-actin network to drive polarized secretion lytic granules, initiating target cell death during adaptive immune response. Branched is generated by nucleation factor actin-related protein 2/3 (Arp2/3) complex. Patients with mutations in complex 1B (ARPC1B) subunit Arp2/3 show combined immunodeficiency, symptoms dysregulation, including recurrent viral infections and reduced CD8+ count. Here, we that loss ARPC1B led CTL cytotoxicity, defect arising at 2 different levels. First, required for lamellipodia formation, migration, actin across synapse. Second, found indispensable maintenance TCR, CD8, GLUT1 membrane proteins plasma CTLs, as recycling via retromer WASH complexes was impaired absence ARPC1B. Loss gave rise defects signaling proliferation upon antigen stimulation ARPC1B-deficient leading a progressive cells. This triggered an activation-induced immunodeficiency activity patients, which could explain susceptibility severe prolonged infections.