Activation of Murine CD4+ and CD8+ T Lymphocytes Leads to Dramatic Remodeling of<i>N</i>-Linked Glycans

Comelli, Elena M.; Sutton-Smith, Mark; Qi, Yuanming; Amado, Margarida; Panico, Maria; Gilmartin, Tim; Whisenant, Thomas; Lanigan, Caroline; Head, Steven R.; Goldberg, David; Morris, Howard R.; Dell, Anne; Paulson, James C.

doi:10.4049/jimmunol.177.4.2431

Cited by 114 publications

(113 citation statements)

References 67 publications

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“…Consequently, the future challenge will be to examine immune responses in primary T-cell subpopulations separated on the basis of ganglioside species. Mouse CD4 + T cells and CD8 + T cells activated by anti-CD3 antibody exhibit different profiles for N-linked glycans (26). In addition, differentially N-glycosylated TCR complexes have been observed in CD4 + T cells compared with CD8 + T cells, which might affect the functional avidity of TCR-transduced T cells (27,28).…”

Section: Discussionmentioning

confidence: 99%

CD4 and CD8 T cells require different membrane gangliosides for activation

Nagafuku

Okuyama²,

Onimaru³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

121

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Initial events of T-cell activation involve movement of the T-cell receptor into lipid rafts. Gangliosides are major components of lipid rafts. While investigating T-cell activation in ganglioside-deficient mice, we observed that CD4 + and CD8 + T cells required different ganglioside subsets for activation. Activation of CD4 + T cells from GM3 synthase-null mice, deficient in GM3-derived gangliosides, is severely compromised, whereas CD8 + T-cell activation is normal. Conversely, in cells from GM2/GD2 synthase-null mice, expressing only GM3 and GD3, CD4 + T-cell activation is normal, whereas CD8 + T-cell activation is deficient. Supplementing the cells with the corresponding missing gangliosides restores normal activation. GM3 synthase-null mice do not develop experimental asthma. Distinct expression patterns of ganglioside species in CD4 + T and CD8 + T cells, perhaps in uniquely functional lipid rafts, define immune functions in each T-cell subset. Control of ganglioside expression would offer a strategy targeting for specific T-cell subpopulations to treat immune diseases.

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Section: Discussionmentioning

confidence: 99%

CD4 and CD8 T cells require different membrane gangliosides for activation

Nagafuku

Okuyama²,

Onimaru³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

121

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“…These variables can dramatically change during thymic-development and peripheral activation and differentiation of T cells. [5,6,18,[38][39][40][41].…”

Section: Galectin-glycoprotein Lattices In T Cell Functionsmentioning

confidence: 99%

Functions of cell surface galectin-glycoprotein lattices

Rabinovich

Toscano

Jackson

et al. 2007

Current Opinion in Structural Biology

361

318

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Programmed remodeling of cell surface glycans by the sequential action of specific glycosyltransferases, can control biological processes by generating or masking ligands for endogenous lectins. Galectins, a family of animal lectins with affinity for β-galactosides, can form multivalent complexes with cell surface glycoconjugates and deliver a variety of intracellular signals to modulate cell activation, differentiation, and survival. Recent efforts involving genetic or biochemical manipulation of O-and N-glycosylation pathways, as well as blockade of the synthesis of endogenous galectins, have illuminated essential roles for galectin-glycoprotein lattices in the control of biological processes including receptor turnover and endocytosis, host-pathogen interactions and immune cell activation and homeostasis.

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“…2, C and D). The presence of sialic acid rules out an alternative biantennary N-glycan terminated by two ␣1,3-galactoses, a structure previously described in T cell blasts (34).…”

Section: Maldi-tof Mass Spectrometry and Hpaec Analysis Of N-glycan Smentioning

confidence: 99%