title: Acid-Triggered Degradable Reagents for Differentiation of Adaptive and Innate Immune Responses to Leishmania-Associated Sugars.
abstract: Lipopolysaccharides (LPS) of Leishmania spp are known to alter innate immune responses. However, the ability of these sugars to specifically alter adaptive T-cell responses is unclear. To study cap sugar-T-cell interactions, pathogen mimics (namely glycodendrimer-coated latex beads with acid-labile linkers) were synthesized. Upon lysosomal acidification, linker breakdown releases glycodendrimers for possible loading on antigen presenting molecules to induce T-cell growth. T-cell proliferation was indeed higher after macrophage exposure to mannobioside or -trioside-containing glycodendrimers than to non-functionalized beads. Yet, blocking phagolysosomal acidification only reduced T-cell proliferation with macrophages exposed to beads with an acid-labile-linker and not to covalently-linked beads. These sugar-modified reagents show that oligosaccharides alone can drive T-cell proliferation by acidification-requiring presentation, most significantly in NKT receptor (CD160)-restricted T cells.
authors.affiliation: Department of Chemistry, Indiana University, Bloomington, IN 47405 (USA) http://www.indiana.edu/∼pohllab/
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Roychoudhury
authors.affiliation: Department of Epidemiology, University of Iowa, Iowa City, IA 52242 (USA).
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Martinez
authors.affiliation: Department of Epidemiology, University of Iowa, Iowa City, IA 52242 (USA).
authors.forename: Tara
authors.initials: T
authors.lastname: Grinnage-Pulley
authors.affiliation: Department of Epidemiology, University of Iowa, Iowa City, IA 52242 (USA).
authors.forename: Robert G
authors.initials: RG
authors.lastname: Schaut
authors.affiliation: Department of Epidemiology, University of Iowa, Iowa City, IA 52242 (USA).
authors.forename: Christine A
authors.initials: CA
authors.lastname: Petersen
authors.affiliation: Department of Chemistry, Indiana University, Bloomington, IN 47405 (USA) http://www.indiana.edu/∼pohllab/. npohl@indiana.edu.
authors.forename: Nicola L B
authors.initials: NL
authors.lastname: Pohl
mesh_terms: D000143:Acids / Q000737:chemistry; D056704:Adaptive Immunity; D017951:Antigen Presentation; D006801:Humans; D007113:Immunity, Innate; D007158:Immunologic Techniques / Q000379:methods; D007202:Indicators and Reagents / Q000737:chemistry; D007891:Leishmania / Q000737:chemistry / Q000276:immunology*; D007896:Leishmaniasis / Q000469:parasitology; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*
chemical_list: D000143:Acids; D007202:Indicators and Reagents; D008070:Lipopolysaccharides
keywords: biological activity; carbohydrates; immunoassays; immunology; leishmania