A Novel Role of Complement Factor C1q in Augmenting the Presentation of Antigen Captured in Immune Complexes to CD8+ T Lymphocytes
2007
Ag-IgG immune complexes (IC) are efficiently taken up, and Ag-derived peptides are subsequently processed and presented by APC. In vitro experiments indicate that IgG Fc Receptors (FcγR) facilitate the efficient uptake of IC by dendritic cells. Previous experiments showed that the cross-presentation of Ag-derived peptides after s.c. administration of IC is FcγR-dependent. To study the role of different FcγR and complement in MHC class I Ag presentation after i.v. administration, we used mice deficient for FcγRs and complement components. These mice were injected with CFSE-labeled OVA-specific CD8+ T cells followed by administration of IC composed of OVA and rabbit anti-OVA IgG i.v. to measure MHC class I presentation of OVA-derived peptides. The Ag presentation was partly reduced in FcRγ-chain-deficient mice, but not affected in FcγRI/II/III-deficient mice, complement factor C3-deficient mice, or FcγRI/II/III × C3-deficient mice. Importantly, CD8+ T cell proliferation was significantly reduced in mice deficient for C1q. This proliferation could be restored when IC were incubated with purified human C1q before injection. Likewise, purified C1q could strongly enhance the uptake and presentation of IC by dendritic cells in vitro. Heat inactivation abrogated the C1q-mediated uptake of IC. In addition, in vivo uptake of OVA-IC in the spleen was significantly reduced in C1q-deficient mice compared with wild-type mice. Together, these results indicate a novel function of C1q, which is present in high levels in the bloodstream, by directly enhancing the uptake and MHC class I presentation of Ag captured in IC by APC to CD8+ T cells.
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