Knockdowns of CD3 zeta chain in Primary NK Cells Illustrate a Critical Role in Antibody-Dependent Cellular Cytotoxicity against Human Immunodeficiency Virus-1
Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B682
Abstract ID: 4986
Presenting Author:
Sho Sugawara , Postdoctoral Research Fellow at Duke Univ. Sch. of Med.
Abstract:
The multifaceted functions of natural killer (NK) cells are critical for suppressing human immunodeficiency virus (HIV)-1 transmission and pathogenesis. Among the diverse activities of NK cells, antibody-dependent cellular cytotoxicity (ADCC) has emerged as a key predictor of successful HIV-1 protection in preclinical vaccine trials as well as in the prevention of mother-to-child transmission. ADCC is initiated when the Fragment crystallizable (Fc) portion of the antibody binds to the Fc receptor, CD16, leading to the phosphorylation of the CD3 zeta chain (CD3z) and Fc receptor gamma chain (FcRg), thereby activating downstream signaling. Despite the fact that CD3z and FcRg were thought to have redundant functions in NK cell ADCC, recent findings suggest that CD3z-mediated signals elicit a more potent ADCC response. However, limited studies have illustrated the direct contribution of CD3z in HIV-1-specific ADCC. To further delineate the roles played by CD3z in HIV-1-specific ADCC, we established a CD3z knockdown system in primary human NK cells. We observed a significant reduction in both general and HIV-1-specific ADCC upon CD3z ablation. In summary, our findings elucidated that CD3z is critical for exerting NK cell ADCC against pathogens including HIV-1, and this dynamic can be applied to the development of NK cell immunotherapeutics against HIV-1 infection and other diseases.
Knockdowns of CD3 zeta chain in Primary NK Cells Illustrate a Critical Role in Antibody-Dependent Cellular Cytotoxicity against Human Immunodeficiency Virus-1
Category
Poster and Podium (Block Symposium)