title: CD205 (DEC-205): a recognition receptor for apoptotic and necrotic self.
abstract: CD205 is an endocytic receptor that is expressed at high levels by cortical thymic epithelial cells and by dendritic cell (DC) subsets, including the splenic CD8+ DC population that is responsible for cross-presentation of apoptotic cell-derived antigens. Antigen endocytosed via CD205 enters the MHC class I and MHC class II antigen presentation pathways and is subsequently presented to both CD4+ and CD8+ T cells. Despite the known role of CD205 in antigen uptake, the nature of the ligands bound by CD205 has not been determined, and most studies have relied on the use of monoclonal antibodies as surrogate ligands. To go beyond this approach, we created a panel of CD205-IgG fusion proteins spanning the extracellular portion of CD205 and used these to identify the physiological distribution of CD205 ligands. Our data demonstrate that two areas of the CD205 molecule, within C-type lectin-like domains (CTLDs) 3+4 and 9+10, recognise ligands expressed during apoptosis and necrosis of multiple cell types, and are additionally expressed by live cells of the dendritic cell line DC2.4. Thus, CD205 acts as a recognition receptor for dying cells, potentially providing an important pathway for the uptake of self-antigen in intrathymic and peripheral tolerance.
authors.affiliation: Department of Immunology, Division of Medicine, Imperial College London, Hammersmith Campus, London W12 0NN, United Kingdom. r.shrimpton@surrey.ac.uk
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Shrimpton
authors.forename: Matt
authors.initials: M
authors.lastname: Butler
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Morel
authors.forename: Efrem
authors.initials: E
authors.lastname: Eren
authors.forename: Swee Shan
authors.initials: SS
authors.lastname: Hue
authors.forename: Mary A
authors.initials: MA
authors.lastname: Ritter
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D017209:Apoptosis / Q000276:immunology* / Q000502:physiology; D002460:Cell Line; D003713:Dendritic Cells / Q000378:metabolism; D004705:Endocytosis; D005260:Female; D007074:Immunoglobulin G / Q000235:genetics; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D009336:Necrosis / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology
chemical_list: D015703:Antigens, CD; C093569:DEC-205 receptor; D007074:Immunoglobulin G; D037181:Lectins, C-Type; D008024:Ligands; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins