Knockdowns of CD3zeta Chain in Primary NK Cells Illustrate Modulation of Antibody-Dependent Cellular Cytotoxicity Against Human Immunodeficiency Virus-1
Publication: AIDS Research and Human Retroviruses
Volume 40, Issue Number 11
Abstract
Multifaceted natural killer (NK) cell activities are indispensable for controlling human immunodeficiency virus (HIV)-1 transmission and pathogenesis. Among the diverse functions of NK cells, antibody-dependent cellular cytotoxicity (ADCC) has been shown to predict better HIV-1 protection. ADCC is initiated by the engagement of an Fc γ receptor CD16 with an Fc portion of the antibody, leading to phosphorylation of the CD3 ζ chain (CD3ζ) and Fc receptor γ chain (FcRγ) as well as downstream signaling activation. Though CD3ζ and FcRγ were thought to have overlapping roles in NK cell ADCC, several groups have reported that CD3ζ-mediated signals trigger a more robust ADCC. However, few studies have illustrated the direct contribution of CD3ζ in HIV-1-specific ADCC. To further understand the roles played by CD3ζ in HIV-1-specific ADCC, we developed a CD3ζ knockdown system in primary human NK cells. We observed that HIV-1-specific ADCC was inhibited by CD3ζ perturbation. In summary, we demonstrated that CD3ζ is important for eliciting HIV-1-specific ADCC, and this dynamic can be utilized for NK cell immunotherapeutics against HIV-1 infection and other diseases.
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Information & Authors
Information
Published In
AIDS Research and Human Retroviruses
Volume 40 • Issue Number 11 • November 2024
Pages: 631 - 636
PubMed: 39041622
Copyright
Copyright 2024, Mary Ann Liebert, Inc., publishers.
History
Published online: 6 November 2024
Published in print: November 2024
Published ahead of print: 8 August 2024
Published ahead of production: 23 July 2024
Topics
Data Availability
The data generated for this study are available upon request to the corresponding author.
Authors
Authors’ Contributions
S.S., R.K.R., and S.J. conceptually developed the initial project, and S.S. performed a majority of experiments. E.L., M.A.C., A.P., S.B.G., and H.B. generated NKCL, and M.A.C. and A.P. helped the expansion of primary human NK cells. K.K. and C.M. developed the protocol for CEM.NKR-CCR5 cell line infection with BaL, prepared the laboratory stock of BaL, and performed HIV-1-specific antibody-titration experiments. Y.L. provided anti-HIV-1 Env antibodies. S.S. and G.W. drafted the article, and all the authors contributed to the final version.
Author Disclosure Statement
All authors report no financial conflicts of interest.
Funding Information
This research was supported by NIH grants: : R01AI161010, R01AI136756, P01AI162242, and, UM1AI164570 (to R.K.R.).
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