title: Selection of phage-displayed human antibody fragments specific for CD1b presenting the Mycobacterium tuberculosis glycolipid Ac2SGL.
abstract: The development of new tools capable of targeting Mycobacterium tuberculosis (Mtb)-infected cells have potential applications in diagnosis, treatment, and prevention of tuberculosis. In Mtb-infected cells, CD1b molecules present Mtb lipids to the immune system (Mtb lipid-CD1b complexes). Because of the lack of CD1b polymorphism, specific Mtb lipid-CD1b complexes could be considered as universal Mtb infection markers. 2-Stearoyl-3-hydroxyphthioceranoyl-2'-sulfate-α-α'-d-trehalose (Ac2SGL) is specific for Mtb, and is not present in other mycobacterial species. The CD1b-Ac2SGL complexes are expressed on the surface of human cells infected with Mtb. The aim of this study was to generate ligands capable of binding these CD1b-Ac2SGL complexes.
  
  
  
  A synthetic human scFv phage antibody library was used to select phage-displayed antibody fragments that recognized CD1b-Ac2SGL using CD1b-transfected THP-1 cells loaded with Ac2SGL.
  
  
  
  One clone, D11-a single, light-variable domain (kappa) antibody (dAbκ11)-showed high relative binding to the Ac2SGL-CD1b complex.
  
  
  
  A ligand recognizing the Ac2SGL-CD1b complex was obtained, which is a potential candidate to be further tested for diagnostic and therapeutic applications.
authors.affiliation: Biologicals Sciences School, University of Concepcion, Chile.
authors.forename: Frank
authors.initials: F
authors.lastname: Camacho
authors.affiliation: School of Health Sciences, Universiti Sains Malaysia, Malaysia; ADAPT Research Cluster, Centre for Research Initiative, Universiti Sains Malaysia, Malaysia.
authors.forename: María E
authors.initials: ME
authors.lastname: Sarmiento
authors.affiliation: Biologicals Sciences School, University of Concepcion, Chile.
authors.forename: Fatima
authors.initials: F
authors.lastname: Reyes
authors.affiliation: University College London, London, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Kim
authors.affiliation: University College London, London, UK.
authors.forename: Jim
authors.initials: J
authors.lastname: Huggett
authors.affiliation: Experimental Immunology, University Hospital, Basel, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Lepore
authors.affiliation: Instituto Finlay, Cuba.
authors.forename: Oscar
authors.initials: O
authors.lastname: Otero
authors.affiliation: CNRS, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France; Université de Toulouse, UPS, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Gilleron
authors.affiliation: CNRS, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France; Université de Toulouse, UPS, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France.
authors.forename: Germain
authors.initials: G
authors.lastname: Puzo
authors.affiliation: School of Health Sciences, Universiti Sains Malaysia, Malaysia; ADAPT Research Cluster, Centre for Research Initiative, Universiti Sains Malaysia, Malaysia; Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Malaysia.
authors.forename: Mohd Nor
authors.initials: MN
authors.lastname: Norazmi
authors.affiliation: University College London, London, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Rook
authors.affiliation: Experimental Immunology, University Hospital, Basel, Switzerland.
authors.forename: Lucia
authors.initials: L
authors.lastname: Mori
authors.affiliation: Experimental Immunology, University Hospital, Basel, Switzerland.
authors.forename: Gennaro
authors.initials: G
authors.lastname: De Libero
authors.affiliation: ADAPT Research Cluster, Centre for Research Initiative, Universiti Sains Malaysia, Malaysia; Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Malaysia. Electronic address: aracosta2001@yahoo.com.
authors.forename: Armando
authors.initials: A
authors.lastname: Acosta
mesh_terms: D000907:Antibodies, Bacterial / Q000235:genetics / Q000276:immunology*; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology*; D001435:Bacteriophages / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006017:Glycolipids / Q000276:immunology*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D057127:Single-Chain Antibodies / Q000235:genetics* / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology
chemical_list: D000907:Antibodies, Bacterial; D018949:Antigens, CD1; C419394:CD1b antigen; D006017:Glycolipids; D057127:Single-Chain Antibodies
keywords: Antibodies; CD1b; Lipids; Tuberculosis