title: Failure of trafficking and antigen presentation by CD1 in AP-3-deficient cells.
abstract: Endocytosed microbial antigens are primarily delivered to lysosomal compartments where antigen binding to MHC and CD1 molecules occurs in an acidic and proteolytically active environment. Signal-dependent delivery to lysosomes has been suggested for these antigen-presenting molecules, but molecular interactions with vesicular coat proteins and adaptors that direct their lysosomal sorting are poorly understood. Here CD1b but not other CD1 isoforms bound the AP-3 adaptor protein complex. In AP-3-deficient cells derived from patients with Hermansky-Pudlak syndrome type 2 (HPS-2), CD1b failed to efficiently gain access to lysosomes, resulting in a profound defect in antigen presentation. Since MHC class II traffics normally in AP-3-deficient cells, defects in CD1b antigen presentation may account for recurrent bacterial infections in HPS-2 patients.
authors.affiliation: Lymphocyte Biology Section, Division of Rheumatology, Immunology and Allergy, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sugita
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Cao
authors.forename: Gerald F M
authors.initials: GF
authors.lastname: Watts
authors.forename: Rick A
authors.initials: RA
authors.lastname: Rogers
authors.forename: Juan S
authors.initials: JS
authors.lastname: Bonifacino
authors.forename: Michael B
authors.initials: MB
authors.lastname: Brenner
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D020816:Amino Acid Motifs; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism; D018949:Antigens, CD1 / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D001424:Bacterial Infections / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D017353:Gene Deletion; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000276:immunology; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D034041:Monomeric Clathrin Assembly Proteins; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport; D013577:Syndrome; D060149:Tetraspanin 30
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000942:Antigens, Bacterial; D015703:Antigens, CD; D018949:Antigens, CD1; C437944:CD1C protein, human; C419394:CD1b antigen; C554586:CD63 protein, human; D002352:Carrier Proteins; D006023:Glycoproteins; D008055:Lipids; D046911:Macromolecular Substances; D008565:Membrane Proteins; D034041:Monomeric Clathrin Assembly Proteins; D010980:Platelet Membrane Glycoproteins; D020033:Protein Isoforms; D060149:Tetraspanin 30; C439023:clathrin assembly protein AP180