A Novel Role of Complement Factor C1q in Augmenting the Presentation of Antigen Captured in Immune Complexes to CD8 super(+) T Lymphocytes

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 (Fc gamma R) facilitate the efficient uptake of IC by dendritic cells. Previous experiments showed that the cross-presen...

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Bibliographic Details
Published in:Journal of Immunology 2007-06, Vol.178 (12), p.7581-7586
Main Authors: van Montfoort, Nadine, de Jong, Judith MH, Schuurhuis, Danita H, van der Voort, Ellen IH, Camps, Marcel GM, Huizinga, Tom WJ, van Kooten, Cees, Daha, Mohamed R, Verbeek, JSjef, Ossendorp, Ferry, Toes, Rene EM
Format: Article
Language:English
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Summary: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 (Fc gamma R) 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 Fc gamma R-dependent. To study the role of different Fc gamma R and complement in MHC class I Ag presentation after i.v. administration, we used mice deficient for Fc gamma Rs and complement components. These mice were injected with CFSE-labeled OVA-specific CD8 super(+) 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 FcR gamma -chain-deficient mice, but not affected in Fc gamma RI/II/III-deficient mice, complement factor C3-deficient mice, or Fc gamma RI/II/III x C3-deficient mice. Importantly, CD8 super(+) 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 super(+) T cells.
ISSN:0022-1767
1365-2567