The MHC class II-associated invariant chain interacts with the neonatal Fc gamma receptor and modulates its trafficking to endosomal/lysosomal compartments.
The neonatal Fc receptor for IgG (FcRn) transfers maternal IgG to the offspring and protects IgG from degradation. The FcRn resides in an acidic intracellular compartment, allowing it to bind IgG. In this study, we found the association of FcRn and invariant chain (Ii). The interaction was initiated within the endoplasmic reticulum by Ii binding to either the FcRn H chain alone or FcRn H chain-beta(2)-microglobulin complex and appeared to be maintained throughout the endocytic pathway. The CLIP in Ii was not required for FcRn-Ii association. The interaction was also detected in IFN-gamma-treated THP-1, epithelial and endothelial cells, and immature mouse DCs. A truncated FcRn without the cytoplasmic tail was unable to traffic to early endosomes; however, its location in early endosomes was restored by Ii expression. FcRn was also detected in the late endosome/lysosome only in the presence of Ii or on exposure to IFN-gamma. In immature human or mouse DCs, FcRn was barely detected in the late endosome/lysosome in the absence of Ii. Furthermore, the cytoplasmic tail of Ii conferred tailless FcRn to route to both the early endosome and late endosome/lysosome in a hybrid molecule. Because the FcRn is expressed in macrophages and DCs or epithelial and endothelial cells where Ii is induced under inflammation and infection, these results reveal the complexity of FcRn trafficking in which Ii is capable of expanding the boundary of FcRn trafficking. Taken together, the intracellular trafficking of FcRn is regulated by its intrinsic sorting information and/or an interaction with Ii chain.
Ye
Lilin
L
Laboratory of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD 20742, USA.
Liu
Xindong
X
Rout
Subrat N
SN
Li
Zili
Z
Yan
Yongqi
Y
Lu
Li
L
Kamala
Tirumalai
T
Nanda
Navreet K
NK
Song
Wenxia
W
Samal
Siba K
SK
Zhu
Xiaoping
X
D000595:Amino Acid Sequence; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016466:CHO Cells; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D011992:Endosomes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019073:HT29 Cells; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D021381:Protein Transport / Q000235:genetics / Q000276:immunology; D011961:Receptors, Fc / Q000378:metabolism*
D000944:Antigens, Differentiation, B-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018836:Inflammation Mediators; D011961:Receptors, Fc; C045084:invariant chain; C100688:Fc receptor, neonatal