Fc γ receptors and the complement system in T cell activation

Abstract

Dendritic Cells (DC) are the major Antigen Presenting Cells (APC) of the immune system that are involved in initiation of CD4+ and CD8+ T cell responses, as DC display many receptors involved in antigen uptake, including several types of FcgammaR. However, other APC, like B cells and macrophages also express FcgammaR and MHC class II molecules. In this thesis we show the contribution of these three different APC, in mice, in the Ag-specific MHC class II restricted activation of CD4+ T cells by systemically administrated Immune Complexes (IC). Furthermore, we analyzed the contribution of FcgammaR and the complement system in the presentation of immune-complexed Ag to CD8+ T cells after intravenous administration of IC. Here C1q appeared to play an important role. Next we aimed at identifying the role and importance of individual Fcgamma-receptors in the initiation and regulation of CD8+ T cell responses after subcutaneous injection of IC. Following this route of application, Fcgamma-receptors appeared to be redundant in the uptake and presentation of immune-complexed Ag. Finally, as mice deficient for C5 are unsusceptible to serum induced arthritis and anti-C5 monoclonal antibody treatment prevents arthritis in mice, the question is addressed whether human RA is also associated with C5.