دورية أكاديمية

Distinct CD16a features on human NK cells observed by flow cytometry correlate with increased ADCC.

التفاصيل البيبلوغرافية
العنوان: Distinct CD16a features on human NK cells observed by flow cytometry correlate with increased ADCC.
المؤلفون: Benavente, Maria C. Rodriguez, Hakeem, Zainab A., Davis, Alexander R., Murray, Nathan B., Azadi, Parastoo, Mace, Emily M., Barb, Adam W.
المصدر: Scientific Reports; 4/4/2024, Vol. 14 Issue 1, p1-14, 14p
مصطلحات موضوعية: KILLER cells, ANTIBODY-dependent cell cytotoxicity, FLOW cytometry, PROCESS capability, MANNOSIDASES
مستخلص: Natural killer (NK) cells destroy tissue that have been opsonized with antibodies. Strategies to generate or identify cells with increased potency are expected to enhance NK cell-based immunotherapies. We previously generated NK cells with increased antibody-dependent cell mediated cytotoxicity (ADCC) following treatment with kifunensine, an inhibitor targeting mannosidases early in the N-glycan processing pathway. Kifunensine treatment also increased the antibody-binding affinity of Fc γ receptor IIIa/CD16a. Here we demonstrate that inhibiting NK cell N-glycan processing increased ADCC. We reduced N-glycan processing with the CRIPSR-CAS9 knockdown of MGAT1, another early-stage N-glycan processing enzyme, and showed that these cells likewise increased antibody binding affinity and ADCC. These experiments led to the observation that NK cells with diminished N-glycan processing capability also revealed a clear phenotype in flow cytometry experiments using the B73.1 and 3G8 antibodies binding two distinct CD16a epitopes. We evaluated this "affinity profiling" approach using primary NK cells and identified a distinct shift and differentiated populations by flow cytometry that correlated with increased ADCC. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:20452322
DOI:10.1038/s41598-024-58541-6