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Doctoral thesis
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Regulation of Innate Immune Cell Function by Fc-gamma Receptor Engagement

Defense date2021-03-18
Abstract

The goal of the current thesis was to elucidate the impact of IgG subclasses on the activation and cytotoxic/phagocytic effector function of Natural Killer cells and Monocytes/Macrophages. More specifically, the influence of individual Fc-gamma receptor repertoires expressed on innate immune cells was assessed. For that, I started by comparing the effect of IgG subclasses on the function of NK cells involved in antibody-coated target cell elimination by FcγRIIIa/CD16 using fresh NK cells. Next, ADCC assays were performed in NK92 cell lines transfected with SNPs for FCGR3A, V158F (rs396991) and L48H/R (rs10127939). Finally, I establish an ADCP assay to further explore interactions between FcγR expressed on Monocytes/macrophages and anti-CD20 monoclonal antibodies leading to phagocytosis. Altogether, these results contribute to clarify the cellular mechanisms that control target cell destruction by ADCC and ADCP, effector cell functions that are highly important for the therapeutic effect of monoclonal antibody therapy.

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Keywords
  • ADCC
  • ADCP
  • Calcium mobilization
  • Daudi
  • FCGR3A polymorphism
  • IgG subclasses
  • Monoclonal antibodies
  • Obinutuzumab
  • Rituximab
  • NK cells
  • NK92
  • Monocytes
  • THP1
Citation (ISO format)
FREITAS MONTEIRO, Marta Cristina. Regulation of Innate Immune Cell Function by Fc-gamma Receptor Engagement. 2021. doi: 10.13097/archive-ouverte/unige:153772
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Creation07/27/2021 2:23:00 PM
First validation07/27/2021 2:23:00 PM
Update time08/07/2023 11:58:54 AM
Status update08/07/2023 11:58:54 AM
Last indexation01/29/2024 10:41:05 PM
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