Dependence of antibody-mediated presentation of antigen on FcRn.
The neonatal Fc receptor for IgG (FcRn) is a distant member of the MHC class I protein family. It binds IgG and albumin in a pH-dependent manner and protects these from catabolism by diverting them from a degradative fate in lysosomes. In addition, FcRn-mediated IgG transport across epithelial barriers is responsible for the transmission of IgG from mother to infant and can also enhance IgG-mediated antigen uptake across mucosal epithelia. We now show a previously undescribed role for FcRn in mediating the presentation of antigens by dendritic cells when antigens are present as a complex with antibody by uniquely directing multimeric immune complexes, but not monomeric IgG, to lysosomes.
Qiao
Shuo-Wang
SW
Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Kobayashi
Kanna
K
Johansen
Finn-Eirik
FE
Sollid
Ludvig M
LM
Andersen
Jan Terje
JT
Milford
Edgar
E
Roopenian
Derry C
DC
Lencer
Wayne I
WI
Blumberg
Richard S
RS
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D006413:Hematopoietic System / Q000166:cytology / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008024:Ligands; D051907:Lysosomal Membrane Proteins / Q000276:immunology; D008247:Lysosomes / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D011961:Receptors, Fc / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D052118:Lysosomal-Associated Membrane Protein 1
D000936:Antigen-Antibody Complex; D006433:Hemocyanins; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D008024:Ligands; D051907:Lysosomal Membrane Proteins; D011961:Receptors, Fc; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C032808:keyhole-limpet hemocyanin; C100688:Fc receptor, neonatal