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

TLDR

Dendritic cells express Fcγ receptors that internalize IgG‑complexed antigens and facilitate efficient MHC class II–restricted antigen presentation. The FcγR‑mediated MHC class I presentation requires proteasomal degradation and functional TAP1‑TAP2 peptide transport. FcγRs induce dendritic cell maturation and promote efficient MHC class I–restricted presentation of exogenous IgG‑complexed antigens, a γ‑chain‑dependent, proteasome‑ and TAP‑dependent process that is highly sensitive in immature DCs and enables potent priming of both CD4+ helper and CD8+ cytotoxic T cells.

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.