Human Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies Do Not Recruit Non-Human Primate CD20+ NK Cells

Abstract

The antibody-dependent cell-mediated cytotoxicity (ADCC) response represents one of mechanisms through which the immune system destroys tumor or infected cells. During the ADCC response to HIV-1, natural killer (NK) cells are recruited by natural infection- or vaccine-induced antibodies (Abs) bound to the HIV-1 envelope glycoproteins expressed on infected CD4+ T cells via Fc-gamma Receptor IIIA (Fc-R IIIA). The NK cells’ Ab-mediated recognition of the infected cells leads to the release of granzymes and perforin by degranulation, triggering apoptotic signal pathways in the infected cells and ultimately leading to their elimination. We have optimized an assay to investigate the degranulation of non-human primate (NHP) NK cells from five different NHP donors by measuring levels of CD107a, a marker present on the inner membranes of NK lysosomes. Using one NHP and two human monoclonal antibodies (mAbs), we compared degranulation of NK in NHP splenocytes, NHP peripheral blood mononuclear cells (PBMC), and human PBMC. We observed that both NHP and human mAbs recruited NHP and human NK effector cells. Of note, we examined the activity of CD20+ and CD20- NK cells, with the former being NK cells from a unique subset of NHP NK splenocytes. Our analysis suggests that CD20+ cells likely do not play a role in the NHP ADCC response. In conclusion, we can identify the cellular populations responsible for the Ab-mediated killing of HIV-1 infected cells, and we will be able to further analyze their full functional profile at the level of messenger RNA expression, i.e. their transcriptomic profile.