Opsonin interactions with immunoglobulin-Fc receptors and their effector functions

Research output: ThesisThesis: Research external, graduation University of Amsterdam

Abstract

This thesis evaluates the role of opsonizing immunoglobulin G (IgG) in cellular destruction through IgG-Fc receptors (FcγRs). In disease settings, IgG features can affect and determine the magnitude of (undesired) functional responses towards target cells, and thus disease severity. Therefore, investigating these factors is of crucial importance in order to elucidate pathophysiology and understand disease manifestation, progression, and outcome.
One of the IgG attributes we address is glycosylation, particularly sialylation and fucosylation, and its effect on FcγR binding capacity and effector functions, respectively. Next to IgG glycosylation, several functional attributes of both effector- and target cells influencing IgG-mediated erythrocyte destruction are studied in detail.
The role of opsonic C-reactive protein (CRP; reportedly elevated and functionally involved in antibody-mediated pathologies) is also studied extensively in the context of IgG-mediated erythrocyte destruction and tumor cell killing. The mechanism underlying CRP’s potentiating effect on IgG-mediated processes is dissected by analyzing the role of FcγRs and IgA-Fc receptor (FcαRI) that have been designated as CRP receptors.
With the emerging knowledge on IgG structure-function relations, the amount of propositions for novel IgG-based therapeutic strategies grew. One promising antibody engineering tool for this is the generation of bispecific antibodies (bsAbs). This thesis describes a novel bsAb format aiming to augment conventional IgG-mediated tumor destruction through additional recruitment of neutrophil effector functions.
In conclusion, this thesis provides cutting-edge information on IgG/CRP-FcR interactions and functional responses. We hope that our findings will add to a better notion of antibody biology and eventually contribute to optimization of antibody-based immunotherapies.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Amsterdam, Netherlands
Supervisors/Advisors
  • van der Schoot, Catherine, Supervisor
  • Vidarsson, Gestur, Co-supervisor
  • van der Schoot, C.E., Supervisor, External person
Award date19 Feb 2021
Print ISBNs9789464191172
Publication statusPublished - 2021

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