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Open AccessJournal ArticleDOI

Fcγ Receptor–mediated Induction of Dendritic Cell Maturation and Major Histocompatibility Complex Class I–restricted Antigen Presentation after Immune Complex Internalization

TLDR
It is shown that FcγRs have two additional specific attributes in murine DCs: the induction of DC maturation and the promotion of efficient MHC class I–restricted presentation of peptides from exogenous, IgG-complexed antigens.
Abstract
Dendritic cells (DCs) express several receptors for the Fc portion of immunoglobulin (Ig)G (FcγR), which mediate internalization of antigen–IgG complexes (immune complexes, ICs) and promote efficient major histocompatibility complex (MHC) class II–restricted antigen presentation. We now show that FcγRs have two additional specific attributes in murine DCs: the induction of DC maturation and the promotion of efficient MHC class I–restricted presentation of peptides from exogenous, IgG-complexed antigens. Both FcγR functions require the FcγR-associated γ chain. FcγR-mediated MHC class I–restricted antigen presentation is extremely sensitive and specific to immature DCs. It requires proteasomal degradation and is dependent on functional peptide transporter associated with antigen processing, TAP1-TAP2. By promoting DC maturation and presentation on both MHC class I and II molecules, ICs should efficiently sensitize DCs for priming of both CD4+ helper and CD8+ cytotoxic T lymphocytes in vivo.

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Citations
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Journal ArticleDOI

Immunobiology of Dendritic Cells

TL;DR: Dendritic cells are antigen-presenting cells with a unique ability to induce primary immune responses and may be important for the induction of immunological tolerance, as well as for the regulation of the type of T cell-mediated immune response.
Journal ArticleDOI

Tolerogenic dendritic cells.

TL;DR: It is suggested that several clinical situations, including autoimmunity and certain infectious diseases, can be influenced by the antigen-specific tolerogenic role of DCs.
Journal ArticleDOI

Fcγ receptors as regulators of immune responses

TL;DR: Recent studies addressing the multifaceted roles of FcRs for IgG (FcγRs) in the immune system are discussed and how this knowledge could be translated into novel therapeutic strategies to treat human autoimmune, infectious or malignant diseases are discussed.
Journal ArticleDOI

Taking dendritic cells into medicine

TL;DR: Some medical implications of DC biology that account for illness and provide opportunities for prevention and therapy are presented.
Journal ArticleDOI

Antigen Presentation and T Cell Stimulation by Dendritic Cells

TL;DR: Dendritic cells take up antigens in peripheral tissues, process them into proteolytic peptides, and load these peptides onto major histocompatibility complex (MHC) class I and II molecules, thus initiating antigen-specific immune responses, or immunological tolerance.
References
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Journal ArticleDOI

Dendritic cells and the control of immunity

TL;DR: Once a neglected cell type, dendritic cells can now be readily obtained in sufficient quantities to allow molecular and cell biological analysis and the realization that these cells are a powerful tool for manipulating the immune system is realized.
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Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha.

TL;DR: Cultured DCs are as efficient as antigen-specific B cells in presenting tetanus toxoid (TT) to specific T cell clones and their efficiency of antigen presentation can be further enhanced by specific antibodies via FcR- mediated antigen uptake.
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T-cell help for cytotoxic T lymphocytes is mediated by CD40–CD40L interactions

TL;DR: In this paper, it was shown that signalling through CD40 can replace CD4+ T-helper cells in priming of helper-dependent CD8+ CTL responses.
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A conditioned dendritic cell can be a temporal bridge between a CD4 + T-helper and a T-killer cell

TL;DR: It is found that the three cells need not meet simultaneously but that the helper cell can first engage and ‘condition’ the dendritic cell, which then becomes empowered to stimulate a killer cell.
Journal ArticleDOI

Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs

TL;DR: It is shown that human dendritic cells, but not macrophages, efficiently present antigen derived from apoptotic cells, stimulating class I-restricted CD8+ CTLs, suggesting a mechanism by which potent APCs acquire antigens from tumours, transplants, infected cells, or even self-tissue, for stimulation or tolerization of C TLs.
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