MHC class I-related FcRn-mediated presentation of immune complexed antigen is associated with endosomal and phagosomal pH and antigen stability in macrophages and dendritic cells (100.56)

Abstract

Abstract The Fc receptors for the immunoglobulin (Ig) G antibody (FcgammaRs) found on macrophages and dendritic cells (DCs) efficiently facilitate the presentation or cross-presentation of immune-complexed (IC)-antigens to T cells. We found that the neonatal Fc receptor for IgG (FcRn) in both macrophages and DCs failed to have a strong effect on the cross-presentation of IC ovalbumin (OVA) antigen to CD8+ T cells. Interestingly, endosomal FcRn enhanced the presentation of the monomeric OVA-IC to OT-II CD4+ T cells robustly, whereas FcRn in phagosomes exerted distinctive effects on antigen presentation between macrophages and DCs. The presentation of phagocytosed latex-OVA-ICs to CD4+ T cells was also considerably enhanced on wild-type versus FcRn-deficient macrophages, 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 below 6.5 in macrophages 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 antigen processing and presentation of ICs to CD4+ T cells in the endosomal versus phagosomal compartments of macrophages versus DCs.