Binding and uptake of agalactosyl IgG by mannose receptor on macrophages and dendritic cells.
Increased levels of agalactosyl IgG (G0 IgG) are found in several autoimmune diseases, including rheumatoid arthritis, in which they are correlated with severity of the disease. To investigate whether structural alteration of IgG may lead to aberrant processing and presentation of IgG peptides as autoantigens, we have studied uptake of G0 IgG by human dendritic cells and macrophages cultured from PBMC. We found that enzymatic removal of terminal galactose residues, which exposes N-acetylglucosamine residues, increases uptake of soluble IgG mediated by mannose receptor on macrophages and dendritic cells. Efficient uptake appears to require recycling of the receptor, can be blocked by saccharides or Abs reactive with mannose receptor, and is dependent upon the state of maturation of the dendritic cells. No differences between IgG isotypes in ability to be internalized by APC were identified, suggesting that uptake would not be limited to a particular subset of Abs. These results suggest a novel pathway by which Abs or Ag-Ab complexes can be taken into dendritic cells and macrophages, and potentially generate epitopes recognized by T cells. These findings may have particular relevance for autoimmune disorders characterized by high levels of G0 IgG.
Dong
X
X
Department of Pathology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, PA 15213, USA.
Storkus
W J
WJ
Salter
R D
RD
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002454:Cell Differentiation / Q000276:immunology; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D004705:Endocytosis / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007132:Immunoglobulin Isotypes / Q000502:physiology; D016130:Immunophenotyping; D037181:Lectins, C-Type; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009005:Monosaccharides / Q000494:pharmacology; D009439:Neuraminidase / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D013997:Time Factors; D001616:beta-Galactosidase / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009005:Monosaccharides; D011956:Receptors, Cell Surface; C064155:agalactosyl IGG; D009439:Neuraminidase; D001616:beta-Galactosidase