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A conserved flagellar pocket exposed high mannose moiety is used by African trypanosomes as a host cytokine binding molecule

(2002) JOURNAL OF BIOLOGICAL CHEMISTRY. 276(36). p.334558-33464
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Abstract
Trypanosomes use antigenic variation of their variant- specific surface glycoprotein (VSG) coat as defense against the host immune system. However, in order to sustain their growth, they need to expose conserved epitopes, allowing host macromolecule binding and receptor-mediated endocytosis. Here we show that Trypanosoma bruce! uses the conserved chitobiose-oligomannose G1(L)CNAc2-Man(5-9)) moieties of its VSG as a binding ligand for tumor necrosis factor TNF), a host cytokine with lectin-like properties. As endocytosis, in trypanosomes is restricted to the flagellar pocket, we show that soluble flagellar pocket extracts, and in particular soluble VSG, inhibit the binding of I-125-TNF to trypanosomes. The interaction between TNF and VSG is confirmed by affinity chromatography, biosensor, and dot-blot affinity measurements, and soluble VSG inhibition of TNF-mediated trypanolysis. In all approaches, removal of N-linked carbohydrates abrogates the TNF-VSG interaction. In addition, synthetic high mannose oligosaccharides can block TNF-VSG interactions, and a VSG glycopeptide carrying the G1(L)CNAc2-Man(5-9) moiety is shown to inhibit TNF-mediated trypanosome killing in mixed parasite macrophage cell cultures. Together, these results support the observation that TNF plays a role in growth control of trypanosomes and, moreover, suggest that, by the use of conserved VSG carbohydrates as lectin-binding epitopes, trypanosomes can limit the necessity to express large numbers of invariant surface exposed receptors.
Keywords
TUMOR-NECROSIS-FACTOR, VARIANT SURFACE GLYCOPROTEINS, FACTOR-ALPHA, TRANSFERRIN-RECEPTOR, LINKED OLIGOSACCHARIDES, BLOOD-STREAM, BRUCEI, RESISTANCE, LECTIN, INTERLEUKIN-2

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Chicago
Magez, Stefan, Magdalena Radwanska, Benoı̂t Stijlemans, Hoang Van Xong, Etienne Pays, and Patrick De Baetselier. 2002. “A Conserved Flagellar Pocket Exposed High Mannose Moiety Is Used by African Trypanosomes as a Host Cytokine Binding Molecule.” Journal of Biological Chemistry 276 (36): 334558–33464.
APA
Magez, S., Radwanska, M., Stijlemans, B., Van Xong, H., Pays, E., & De Baetselier, P. (2002). A conserved flagellar pocket exposed high mannose moiety is used by African trypanosomes as a host cytokine binding molecule. JOURNAL OF BIOLOGICAL CHEMISTRY, 276(36), 334558–33464.
Vancouver
1.
Magez S, Radwanska M, Stijlemans B, Van Xong H, Pays E, De Baetselier P. A conserved flagellar pocket exposed high mannose moiety is used by African trypanosomes as a host cytokine binding molecule. JOURNAL OF BIOLOGICAL CHEMISTRY. 2002;276(36):334558–33464.
MLA
Magez, Stefan et al. “A Conserved Flagellar Pocket Exposed High Mannose Moiety Is Used by African Trypanosomes as a Host Cytokine Binding Molecule.” JOURNAL OF BIOLOGICAL CHEMISTRY 276.36 (2002): 334558–33464. Print.
@article{8528996,
  abstract     = {Trypanosomes use antigenic variation of their variant- specific surface glycoprotein (VSG) coat as defense against the host immune system. However, in order to sustain their growth, they need to expose conserved epitopes, allowing host macromolecule binding and receptor-mediated endocytosis. Here we show that Trypanosoma bruce! uses the conserved chitobiose-oligomannose G1(L)CNAc2-Man(5-9)) moieties of its VSG as a binding ligand for tumor necrosis factor TNF), a host cytokine with lectin-like properties. As endocytosis, in trypanosomes is restricted to the flagellar pocket, we show that soluble flagellar pocket extracts, and in particular soluble VSG, inhibit the binding of I-125-TNF to trypanosomes. The interaction between TNF and VSG is confirmed by affinity chromatography, biosensor, and dot-blot affinity measurements, and soluble VSG inhibition of TNF-mediated trypanolysis. In all approaches, removal of N-linked carbohydrates abrogates the TNF-VSG interaction. In addition, synthetic high mannose oligosaccharides can block TNF-VSG interactions, and a VSG glycopeptide carrying the G1(L)CNAc2-Man(5-9) moiety is shown to inhibit TNF-mediated trypanosome killing in mixed parasite macrophage cell cultures. Together, these results support the observation that TNF plays a role in growth control of trypanosomes and, moreover, suggest that, by the use of conserved VSG carbohydrates as lectin-binding epitopes, trypanosomes can limit the necessity to express large numbers of invariant surface exposed receptors.},
  author       = {Magez, Stefan and Radwanska, Magdalena and Stijlemans, Beno{\i}\unmatched{0302}t and Van Xong, Hoang and Pays, Etienne and De Baetselier, Patrick},
  issn         = {0021-9258},
  journal      = {JOURNAL OF BIOLOGICAL CHEMISTRY},
  language     = {eng},
  number       = {36},
  pages        = {334558--33464},
  title        = {A conserved flagellar pocket exposed high mannose moiety is used by African trypanosomes as a host cytokine binding molecule},
  url          = {http://dx.doi.org/10.1074/jbc.m103412200},
  volume       = {276},
  year         = {2002},
}

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