Surface CD16 Modulation by Toll-Like Receptor 9 (TLR9) Agonism on Human Natural Killer Cells
Presenter Type
UNO Undergraduate Student
Major/Field of Study
Biology
Other
Molecular and Biomedical Biology
Advisor Information
Department of Biology, Assistant Professor, PhD
Location
CEC RM #127
Presentation Type
Oral Presentation
Start Date
22-3-2024 10:30 AM
End Date
22-3-2024 11:45 AM
Abstract
Human CD16, a Fc-gamma-III receptor, binds to the constant fragment (Fc) of IgG (gamma) antibodies and leaves the Fab, or antigen-binding fragment, ends of the antibody free to bind to its specific antigen. An antibody’s structure is associated with a Y-shape. The two binding sites at the top of this “Y” are the Fab ends and the singular binding region at the bottom is the Fc end. When one or both the Fab binds to its specific target, the Fc is free to bind to an Fc receptor. This series of bindings is critical for a killing mechanism mediated by human natural killer (NK) cells called antibody-dependent cell-mediated cytotoxicity (ADCC). In NK cell-mediated ADCC, an IgG antibody’s Fab binds to a pathogenic cell’s marker while the Fc binds to a Fc receptor on a NK cell. In the Denton Immunobiology Laboratory, we observed an unexpected circumstance where an immunotherapy drug, a toll-like receptor 9 (TLR9) agonist, reduced CD16 surface levels on NK cells. Due to this reduction, the immunotherapy did not boost the NK cells’ ability to perform ADCC as suggested by other research groups in prior publications. In this talk, data will be presented regarding the impact of TLR9 agonism on CD16 expression and how this could be relevant for the use of TLR9 agonism in anti-cancer clinical contexts.
Surface CD16 Modulation by Toll-Like Receptor 9 (TLR9) Agonism on Human Natural Killer Cells
CEC RM #127
Human CD16, a Fc-gamma-III receptor, binds to the constant fragment (Fc) of IgG (gamma) antibodies and leaves the Fab, or antigen-binding fragment, ends of the antibody free to bind to its specific antigen. An antibody’s structure is associated with a Y-shape. The two binding sites at the top of this “Y” are the Fab ends and the singular binding region at the bottom is the Fc end. When one or both the Fab binds to its specific target, the Fc is free to bind to an Fc receptor. This series of bindings is critical for a killing mechanism mediated by human natural killer (NK) cells called antibody-dependent cell-mediated cytotoxicity (ADCC). In NK cell-mediated ADCC, an IgG antibody’s Fab binds to a pathogenic cell’s marker while the Fc binds to a Fc receptor on a NK cell. In the Denton Immunobiology Laboratory, we observed an unexpected circumstance where an immunotherapy drug, a toll-like receptor 9 (TLR9) agonist, reduced CD16 surface levels on NK cells. Due to this reduction, the immunotherapy did not boost the NK cells’ ability to perform ADCC as suggested by other research groups in prior publications. In this talk, data will be presented regarding the impact of TLR9 agonism on CD16 expression and how this could be relevant for the use of TLR9 agonism in anti-cancer clinical contexts.