title: Generation of CD1 tetramers as a tool to monitor glycolipid-specific T cells.
abstract: CD1 molecules are beta(2)m-associated HLA class-I-like glycoproteins which have the unique ability to present glycolipid and phospholipid antigens to specific T lymphocytes. To study the biology of CD1 and its role in human disease we developed novel techniques for generation of recombinant CD1/lipid complexes by in vitro refolding. Fluorescent tetrameric complexes made from soluble recombinant CD1d/alpha-galactosylceramide complexes allowed highly sensitive and specific ex vivo and in vitro detection and functional characterization of novel human T-lymphocyte populations. Furthermore, protein crystals were obtained from soluble recombinant CD1b/beta(2)m-proteins loaded either with phosphatidylinositol or ganglioside GM2, which led to the first atomic structure determination of a CD1/lipid complex. The analysis of these crystal structures clarified how CD1b molecules can bind lipid ligands of different size, and revealed a broader spectrum of potential CD1b ligands than previously predicted.
authors.affiliation: Tumour Immunology Unit, The Weatherall Institute of Molecular Medicine, University of Oxford, UK.
authors.forename: Stephan D
authors.initials: SD
authors.lastname: Gadola
authors.forename: Anastasios
authors.initials: A
authors.lastname: Karadimitris
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Zaccai
authors.forename: Mariolina
authors.initials: M
authors.lastname: Salio
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dulphy
authors.forename: Dawn
authors.initials: D
authors.lastname: Shepherd
authors.forename: E Yvonne
authors.initials: EY
authors.lastname: Jones
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000737:chemistry / Q000276:immunology*; D006017:Glycolipids / Q000276:immunology*; D006801:Humans; D020836:Protein Structure, Quaternary; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018949:Antigens, CD1; D006017:Glycolipids