title: Antigen cross-presentation of immune complexes.
abstract: The ability of dendritic cells (DCs) to cross-present tumor antigens has long been a focus of interest to physicians, as well as basic scientists, that aim to establish efficient cell-based cancer immune therapy. A prerequisite for exploiting this pathway for therapeutic purposes is a better understanding of the mechanisms that underlie the induction of tumor-specific cytotoxic T-lymphocyte (CTL) responses when initiated by DCs via cross-presentation. The ability of humans DC to perform cross-presentation is of utmost interest, as this cell type is a main target for cell-based immunotherapy in humans. The outcome of a cross-presentation event is guided by the nature of the antigen, the form of antigen uptake, and the subpopulation of DCs that performs presentation. Generally, CD8α(+) DCs are considered to be the most potent cross-presenting DCs. This paradigm, however, only applies to soluble antigens. During adaptive immune responses, immune complexes form when antibodies interact with their specific epitopes on soluble antigens. Immunoglobulin G (IgG) immune complexes target Fc-gamma receptors on DCs to shuttle exogenous antigens efficiently into the cross-presentation pathway. This receptor-mediated cross-presentation pathway is a well-described route for the induction of strong CD8(+) T cell responses. IgG-mediated cross-presentation is intriguing because it permits the CD8(-) DCs, which are commonly considered to be weak cross-presenters, to efficiently cross-present. Engaging multiple DC subtypes for cross-presentation might be a superior strategy to boost CTL responses in vivo. We here summarize our current understanding of how DCs use IgG-complexed antigens for the efficient induction of CTL responses. Because of its importance for human cell therapy, we also review the recent advances in the characterization of cross-presentation properties of human DC subsets.
authors.affiliation: Department of Pediatrics, Division of Gastroenterology and Nutrition, Boston Children's Hospital, Harvard Medical School , Boston, MA , USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Platzer
authors.affiliation: Department of Pediatrics, Division of Gastroenterology and Nutrition, Boston Children's Hospital, Harvard Medical School , Boston, MA , USA.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Stout
authors.affiliation: Department of Pediatrics, Division of Gastroenterology and Nutrition, Boston Children's Hospital, Harvard Medical School , Boston, MA , USA.
authors.forename: Edda
authors.initials: E
authors.lastname: Fiebiger
keywords: CD8+ T cell priming; DC subset functions; Fc receptor-mediated antigen uptake; IgG-complexed antigens; anti-tumor immune responses; cell type-specific cross-presentation
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