Antigen handling and cross-presentation by dendritic cells

Ho, N.I.S.C. (2020)

Doctoral Thesis

In the current thesis, we provide novel insights in antigen uptake, storage, processing, and sustained cross-presentation mechanisms in dendritic cells (DCs) in vitro and in vivo. We have studied antigen handling functions by dendritic cells in three different antigen delivery routes: antibody targeting involving Fcγ receptors and complement factor C1q, C-type lectin receptor targeting, and toll-like receptor ligand targeting systems. Our data highlights that antigen storage in specialized compartments in DCs, despite the chosen uptake route, is beneficial for prolonged antigen cross-presentation by DCs and sustained T cell activation. Further in vivo studies in different antigen presenting cell (APC) subsets confirmed the presence of antigen storage compartments by isolating APC subsets after in vivo antigen uptake. Besides, we revealed a dominant role of C1q in antigen-antibody immune complex uptake and cross-presentation in vivo in contrast to the crucial role of Fcγ receptors in vitro. Furthermore, we demonstrated that autophagosomes have a negative impact on the storage of antigen in those specialized compartments and thereby affecting DC cross-presentation efficiency. With the current studies, we unraveled some mechanics of antigen processing in DCs which contribute to future vaccine designs against diseases such as cancer.

• Dendritic cells
• Cross-presentation
• Fcγ receptors
• C-type lectin receptors
• Toll-like receptors
• Antigen presenting cells
• Autophagy
• C1q
• Synthetic-long peptide conjugates
• Immune complexes

• All authors: Ho, N.I.S.C.
• Supervisor: Ossendorp, F.A.
• Co-supervisor: Fillipov, D.V.
• Committee: Borst, J.G.; Neefjes, J.J.C.; Haan, J.M.M. den; Kasteren, S.I. van
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2020-07-09
• ISBN (print): 9789463759243