title: Molecular interaction of CD1b with lipoglycan antigens.
abstract: The ability of human CD1b molecules to present nonpeptide antigens is suggested by the T cell recognition of microbial lipids and lipoglycans in the presence of CD1b-expressing antigen-presenting cells. We demonstrate the high-affinity interaction of CD1b molecules with the acyl side chains of known T cell antigens, lipoarabinomannan, phosphatidylinositol mannoside, and glucose monomycolate. Furthermore, CD1b-antigen binding was optimal at acidic pH, consistent with the known requirement for endosomal acidification in CD1b-restricted antigen presentation. The mechanism for CD1b-ligand interaction involves the partial unfolding of the alpha helices of CD1b at acidic pH, revealing a hydrophobic binding site that could accommodate lipid. These data provide direct evidence that the CD1b molecule has evolved unique biochemical properties that enable the binding of lipid-containing antigens from intracellular pathogens.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90095, USA.
authors.forename: W A
authors.initials: WA
authors.lastname: Ernst
authors.forename: J
authors.initials: J
authors.lastname: Maher
authors.forename: S
authors.initials: S
authors.lastname: Cho
authors.forename: K R
authors.initials: KR
authors.lastname: Niazi
authors.forename: D
authors.initials: D
authors.lastname: Chatterjee
authors.forename: D B
authors.initials: DB
authors.lastname: Moody
authors.forename: G S
authors.initials: GS
authors.lastname: Besra
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: P E
authors.initials: PE
authors.lastname: Jensen
authors.forename: S A
authors.initials: SA
authors.lastname: Porcelli
authors.forename: M
authors.initials: M
authors.lastname: Kronenberg
authors.forename: R L
authors.initials: RL
authors.lastname: Modlin
mesh_terms: D000817:Anilino Naphthalenesulfonates; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology*; D006017:Glycolipids / Q000276:immunology; D006863:Hydrogen-Ion Concentration; D008070:Lipopolysaccharides / Q000276:immunology*; D009166:Mycobacterium leprae / Q000276:immunology; D010716:Phosphatidylinositols / Q000276:immunology; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000276:immunology; D013050:Spectrometry, Fluorescence; D001613:beta 2-Microglobulin / Q000276:immunology*
chemical_list: D000817:Anilino Naphthalenesulfonates; D000942:Antigens, Bacterial; D018949:Antigens, CD1; D006017:Glycolipids; D008070:Lipopolysaccharides; D010716:Phosphatidylinositols; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; C048938:glucose mycolate; C050016:lipoarabinomannan; C034154:phosphatidylinositol mannoside; C027132:1-anilino-8-naphthalenesulfonate