title: CD1a and CD1b surface expression is independent from de novo synthesized glycosphingolipids.
abstract: CD1 molecules resemble classical MHC molecules in structure, bind self and bacterial glycolipids and present them to T cells. Whether the CD1 antigen-binding groove becomes filled during maturation and traffic to the cell surface is an important and still unsolved biological question. As most cell types synthesize complex glycosphingolipids (GSL), which also stimulate CD1-restricted T cells, it could be possible that these ligands associate with nascent CD1 molecules. Here, we show that treatment of cells with drugs blocking at different levels the de novo and salvage pathways of GSL synthesis does not prevent surface expression of CD1a and CD1b. Furthermore, transfection of CD1A and CD1B genes in a mutant cell line unable to synthesize glucosylceramides and galactosylceramides showed normal surface expression of both CD1 molecules. Lack of GSL did not induce intracellular CD1 accumulation as indicated by confocal microscopy. The same results were obtained by transfecting the Lec series of mutants, which are deficient in sugar addition to glycolipids and glycoproteins. These findings demonstrate that endogenous de novo synthesized GSL are not mandatory for CD1a and CD1b negotiating surface expression.
authors.affiliation: Experimental Immunology, Department of Research, University Hospital, Basel, Switzerland.
authors.forename: Vania
authors.initials: V
authors.lastname: Manolova
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hirabayashi
authors.forename: Lucia
authors.initials: L
authors.lastname: Mori
authors.forename: Gennaro
authors.initials: G
authors.lastname: De Libero
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism*; D050260:Carbohydrate Metabolism; D002455:Cell Division; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006028:Glycosphingolipids / Q000096:biosynthesis / Q000378:metabolism*; D016695:Glycosyltransferases / Q000172:deficiency; D051379:Mice; D018613:Microscopy, Confocal; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D018949:Antigens, CD1; C419393:CD1a antigen; C419394:CD1b antigen; D006028:Glycosphingolipids; D016695:Glycosyltransferases