title: CD1 molecules efficiently present antigen in immature dendritic cells and traffic independently of MHC class II during dendritic cell maturation.
abstract: Upon exposure to Ag and inflammatory stimuli, dendritic cells (DCs) undergo a series of dynamic cellular events, referred to as DC maturation, that involve facilitated peptide Ag loading onto MHC class II molecules and their subsequent transport to the cell surface. Besides MHC molecules, human DCs prominently express molecules of the CD1 family (CD1a, -b, -c, and -d) and mediate CD1-dependent presentation of lipid and glycolipid Ags to T cells, but the impact of DC maturation upon CD1 trafficking and Ag presentation is unknown. Using monocyte-derived immature DCs and those stimulated with TNF-alpha for maturation, we observed that none of the CD1 isoforms underwent changes in intracellular trafficking that mimicked MHC class II molecules during DC maturation. In contrast to the striking increase in surface expression of MHC class II on mature DCs, the surface expression of CD1 molecules was either increased only slightly (for CD1b and CD1c) or decreased (for CD1a). In addition, unlike MHC class II, DC maturation-associated transport from lysosomes to the plasma membrane was not readily detected for CD1b despite the fact that both molecules were prominently expressed in the same MIIC lysosomal compartments before maturation. Consistent with this, DCs efficiently presented CD1b-restricted lipid Ags to specific T cells similarly in immature and mature DCs. Thus, DC maturation-independent pathways for lipid Ag presentation by CD1 may play a crucial role in host defense, even before DCs are able to induce maximum activation of peptide Ag-specific T cells.
authors.affiliation: Lymphocyte Biology Section, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Cao
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sugita
authors.forename: Nicole
authors.initials: N
authors.lastname: Van Der Wel
authors.forename: Jean
authors.initials: J
authors.lastname: Lai
authors.forename: Rick A
authors.initials: RA
authors.lastname: Rogers
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Peters
authors.forename: Michael B
authors.initials: MB
authors.lastname: Brenner
mesh_terms: D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000648:ultrastructure; D006017:Glycolipids / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D021381:Protein Transport / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D018949:Antigens, CD1; C419394:CD1b antigen; D006017:Glycolipids; D000949:Histocompatibility Antigens Class II; D013745:Tetanus Toxoid; D014409:Tumor Necrosis Factor-alpha; C048938:glucose mycolate