Title

The neonatal FcR-mediated presentation of immune-complexed antigen is associated with endosomal and phagosomal pH and antigen stability in macrophages and dendritic cells.

Document Type

Article

Publication Date

2011

Keywords

Antigen-Presentation, Antigens, Blotting-Western, Cell-Proliferation, Cells-Cultured, Cross-Priming, Dendritic-Cells, Endocytosis, Endosomes, Female, Flow-Cytometry, Histocompatibility-Antigens-Class-I, Hydrogen-Ion-Concentration, Immunoglobulin-G, Macrophages, Mice-Inbred-C57BL, Mice-Knockout, Mice-Transgenic, Ovalbumin, Phagosomes, Protein-Binding, Receptors-Fc, T-Lymphocytes

JAX Source

J Immunol 2011; 186(8):4674-86.

Abstract

The FcgammaRs found on macrophages (Ms) and dendritic cells (DCs) efficiently facilitate the presentation or cross-presentation of immune-complexed Ags to T cells. We found that the MHC class I-related neonatal FcR for IgG (FcRn) in both Ms and DCs failed to have a strong effect on the cross-presentation of immune complex (IC) OVA Ag to CD8(+) T cells. Interestingly, endosomal FcRn enhanced the presentation of the monomeric OVA-IC to CD4(+) T cells robustly, whereas FcRn in phagosomes exerted distinctive effects on Ag presentation between Ms and DCs. The presentation of phagocytosed OVA-ICs to CD4(+) T cells was considerably enhanced on wild-type versus FcRn-deficient Ms, but was not affected in FcRn-deficient DCs. This functional discrepancy was associated with the dependence of IgG-FcRn binding in an acidic pH. Following phagocytosis, the phagosomal pH dropped rapidly to <6.5 in Ms but remained in the neutral range in DCs. This disparity in pH determined the rate of degradation of phagocytosed ICs. Thus, our findings reveal that FcRn expression has a different effect on Ag processing and presentation of ICs to CD4(+) T cells in the endosomal versus phagosomal compartments of Ms versus DCs.

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