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.
First Page
4674
Last Page
4686
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.
Recommended Citation
Liu X,
Lu L,
Yang Z,
Palaniyandi S,
Zeng R,
Gao LY,
Mosser DM,
Roopenian DC,
Zhu X.
The neonatal FcR-mediated presentation of immune-complexed antigen is associated with endosomal and phagosomal pH and antigen stability in macrophages and dendritic cells. J Immunol 2011; 186(8):4674-86.