van Montfoort Nadine, de Jong Judith M H, Schuurhuis Danita H, van der Voort Ellen I H, Camps Marcel G M, Huizinga Tom W J, van Kooten Cees, Daha Mohamed R, Verbeek J Sjef, Ossendorp Ferry, Toes René E M
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands.
J Immunol. 2007 Jun 15;178(12):7581-6. doi: 10.4049/jimmunol.178.12.7581.
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 (FcgammaR) 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 FcgammaR-dependent. To study the role of different FcgammaR and complement in MHC class I Ag presentation after i.v. administration, we used mice deficient for FcgammaRs 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 FcRgamma-chain-deficient mice, but not affected in FcgammaRI/II/III-deficient mice, complement factor C3-deficient mice, or FcgammaRI/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.
Ag-IgG免疫复合物（IC）能被有效摄取，随后抗原衍生肽由抗原呈递细胞（APC）进行加工和呈递。体外实验表明，IgG Fc受体（FcγR）促进树突状细胞对IC的有效摄取。先前的实验表明，皮下注射IC后抗原衍生肽的交叉呈递依赖于FcγR。为了研究静脉注射后不同FcγR和补体在MHC I类抗原呈递中的作用，我们使用了缺乏FcγR和补体成分的小鼠。给这些小鼠注射CFSE标记的卵清蛋白（OVA）特异性CD8 + T细胞，随后静脉注射由OVA和兔抗OVA IgG组成的IC，以检测OVA衍生肽的MHC I类呈递情况。在FcRγ链缺陷小鼠中，抗原呈递部分降低，但在FcγRI/II/III缺陷小鼠、补体因子C3缺陷小鼠或FcγRI/II/III×C3缺陷小鼠中未受影响。重要的是，在缺乏C1q的小鼠中，CD8 + T细胞增殖显著降低。当IC在注射前与纯化的人C1q孵育时，这种增殖可以恢复。同样，纯化的C1q在体外可强烈增强树突状细胞对IC的摄取和呈递。热灭活消除了C1q介导的IC摄取。此外，与野生型小鼠相比，C1q缺陷小鼠脾脏中OVA-IC的体内摄取显著降低。总之，这些结果表明，血液中高水平存在的C1q具有一种新功能，即通过直接增强APC捕获的IC中抗原对CD8 + T细胞的摄取和MHC I类呈递。
