Laboratory of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.
J Immunol. 2011 Apr 15;186(8):4674-86. doi: 10.4049/jimmunol.1003584. Epub 2011 Mar 14.
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.
巨噬细胞 (Ms) 和树突状细胞 (DCs) 上发现的 FcγRs 可有效地促进免疫复合物化抗原向 T 细胞的呈递或交叉呈递。我们发现，Ms 和 DCs 中的 IgG 相关的新生 Fc 受体 (FcRn) 对免疫复合物 (IC) OVA 抗原向 CD8(+) T 细胞的交叉呈递没有强烈影响。有趣的是，内体 FcRn 可显著增强单体 OVA-IC 向 CD4(+) T 细胞的呈递，而吞噬体中的 FcRn 在 Ms 和 DCs 之间对 Ag 呈递有不同的影响。与 FcRn 缺陷型 Ms 相比，野生型 Ms 吞噬的 OVA-IC 向 CD4(+) T 细胞的呈递显著增强，但在 FcRn 缺陷型 DC 中没有影响。这种功能差异与 IgG-FcRn 结合在酸性 pH 值下的依赖性有关。吞噬作用后，Ms 中的吞噬体 pH 值迅速降至 <6.5，但在 DC 中仍保持中性范围。这种 pH 值的差异决定了吞噬的 IC 降解的速度。因此，我们的研究结果表明，FcRn 表达对 Ms 与 DC 中内体与吞噬体隔间中 IC 向 CD4(+) T 细胞的 Ag 加工和呈递有不同的影响。
