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.
abstract: The FcγRs 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.
authors.affiliation: Laboratory of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.
authors.forename: Xindong
authors.initials: X
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Lu
authors.forename: Ziyan
authors.initials: Z
authors.lastname: Yang
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Palaniyandi
authors.forename: Rongyu
authors.initials: R
authors.lastname: Zeng
authors.forename: Lian-Yong
authors.initials: LY
authors.lastname: Gao
authors.forename: David M
authors.initials: DM
authors.lastname: Mosser
authors.forename: Derry C
authors.initials: DC
authors.lastname: Roopenian
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004705:Endocytosis / Q000276:immunology; D011992:Endosomes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010588:Phagosomes / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D000941:Antigens; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; D010047:Ovalbumin; C100688:Fc receptor, neonatal