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* Department of Immunohematology and Blood Transfusion;
Department of Rheumatology;
Department of Nephrology; and
Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
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
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 FcR-dependent. To study the role of different FcR and complement in MHC class I Ag presentation after i.v. administration, we used mice deficient for FcRs 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 FcR-chain-deficient mice, but not affected in FcRI/II/III-deficient mice, complement factor C3-deficient mice, or FcRI/II/III x 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the following grants: Dutch Cancer Society UL 2004-3008 (to N.v.M.), The Netherlands Organisation for Scientific Research (NOW) 901-07-249 (to J.M.H.d.J.), and VIDI (to R.E.M.T.).
2 N.v.M. and J.M.H.d.J. equally contributed to this work.
3 J.S.V., F.O., and R.E.M.T. equally contributed to this work.
4 Address correspondence and reprint requests to Dr. Ferry Ossendorp, Leiden University, Albinusdreef 2, Leiden, The Netherlands. E-mail address: F.A.Ossendorp{at}lumc.nl
5 Abbreviations used in this paper: DC, dendritic cells; FcR, IgG Fc receptors; OVA-IC, OVA-anti-OVA IgG immune complexes; IC, immune complexes; B6, C57BL/6Kh; WT, wild-type; KO, knockout; rIgG
OVA, OVA-specific rabbit IgG; hC1q, human-derived C1q; OVA-Alexa488, Alexa Fluor488-conjugated OVA.
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