Author ORCID Identifier

0009-0001-6874-3498

Month/Year of Graduation

12-2024

Degree Name

Bachelor of Science (B.S.)

Department

Biology

First Advisor

Paul W. Denton

Abstract

In the Denton Immunobiology Laboratory, we observed an unexpected circumstance when human peripheral blood mononuclear cells (PBMCs) were exposed to an immunotherapy drug, a toll-like receptor 9 (TLR9) agonist, leading to reduced surface CD16a levels on a specific subset of PBMCs, human natural killer (NK) cells [4]. To kill pathogenic cells, NK cells have two distinct killing methods: direct killing – not the subject of this proposal – and antibody- dependent cell-mediated cytotoxicity (ADCC). ADCC requires antibodies to help the NK cells recognize diseased cells and both ends of the antibody must be engaged. The antigen binding fragment (Fab) binds to a molecule on the pathogenic cell while the other end, the constant fragment (Fc), binds to an Fc receptor. Human CD16a, a Fc𝛾III receptor, is a binding site for the Fc of IgG antibodies (which are used in our experiment). The series of bindings is critical for human NK cell-mediated ADCC. Due to the reduction of CD16a levels on the human NK cells, the immunotherapy did not boost NK cell-mediated ADCC as suggested by other researchers in prior publications [9, 10, 15, 16, 17, 20]. This thesis project will study the changes in surface CD16a levels on NK cells over time after the introduction of TLR9 agonism. Other specific findings are not in the abstract since they are redacted from the paper due to material transfer agreement requirements.

Available for download on Thursday, April 15, 3024

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