title: The bovine CD1D gene has an unusual gene structure and is expressed but cannot present α-galactosylceramide with a C26 fatty acid.
abstract: Although CD1d and NKT cells have been proposed to have highly conserved functions in mammals, data on functions of CD1d and NKT cells in species other than humans and rodents are lacking. Upon stimulation with the CD1d-presented synthetic antigen α-galactosylceramide, human and rodent type I invariant NKT cells release large amounts of cytokines. The two bovine CD1D (boCD1D) genes have structural features that suggest that they cannot be translated into functional proteins expressed on the cell surface. Here we provide evidence that despite an intron-exon structure and signal peptide that are different from all other known CD1 genes, boCD1D can be translated into a protein that is expressed on the cell surface. However, in vivo treatment of cattle (Bos taurus) with 0.1, 1, or 10 µg kg⁻¹ of the most commonly used α-galactosylceramide, which has a C26 fatty acid, did not lead to an increase in body temperature and serum cytokine levels of the animals. This lack of reactivity is not due to a complete inability of boCD1d to present glycosphingolipids because α-galactosylceramide variants with shorter fatty acids could be presented by boCD1d to human NKT cells in vitro. This suggests that the natural ligands of boCD1d are smaller lipids.
authors.affiliation: Department of Infectious Diseases and Immunology, Universiteit Utrecht, Yalelaan 1, 3584CL Utrecht, The Netherlands.
authors.forename: Thi Kim Anh
authors.initials: TK
authors.lastname: Nguyen
authors.forename: Ad P
authors.initials: AP
authors.lastname: Koets
authors.forename: Martin
authors.initials: M
authors.lastname: Vordermeier
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Jervis
authors.forename: Liam R
authors.initials: LR
authors.lastname: Cox
authors.forename: Simon P
authors.initials: SP
authors.lastname: Graham
authors.forename: Wiebren J
authors.initials: WJ
authors.lastname: Santema
authors.forename: D Branch
authors.initials: DB
authors.lastname: Moody
authors.forename: Serge
authors.initials: S
authors.lastname: van Calenbergh
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Zajonc
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Ildiko
authors.initials: I
authors.lastname: Van Rhijn
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D001483:Base Sequence; D001831:Body Temperature; D002417:Cattle; D002460:Cell Line; D016207:Cytokines / Q000097:blood; D005227:Fatty Acids / Q000737:chemistry* / Q000276:immunology; D005699:Galactosylceramides / Q000737:chemistry* / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology
chemical_list: D055610:Antigens, CD1d; D016207:Cytokines; D005227:Fatty Acids; D005699:Galactosylceramides; D008024:Ligands; C493154:alpha-galactosylceramide