Acid‐Triggered Degradable Reagents for Differentiation of Adaptive and Innate Immune Responses to Leishmania‐Associated Sugars1. (19th June 2015)

• Record Type: Journal Article
• Authors: Roychoudhury, Rajarshi; Martinez, Pedro A.; Grinnage‐Pulley, Tara; Schaut, Robert G.; Petersen, Christine A.; Pohl, Nicola L. B.
• Is Part Of: Angewandte Chemie. Volume 127:Number 33(2015)
• Page Start: 9746
• Page End: 9749
• Publication Date: 2015-06-19
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201502807
• Languages: English
• ISSNs: 0044-8249

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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.</p> </abstract>