2012
DOI: 10.1073/pnas.1114965109
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CD4 and CD8 T cells require different membrane gangliosides for activation

Abstract: 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 … Show more

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Cited by 122 publications
(98 citation statements)
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“…The essential proximal TCR signaling molecules LCK and LAT reside in different lipid raft subsets that fuse upon TCR stimulation (33), and the interaction of TCR-associated signaling molecules (including LCK, LFA1, and PI3K) with GM3 or GM1 induces differential recruitment of downstream signaling targets that affect T cell function (34,35). Moreover, recent reports show that CD4 + and CD8 + T cells exclusively require a-series and o-series GSLs, respectively, for TCR-mediated activation (8,36). The reduction of cellular GSL levels by pharmacological means or by disruption of GM3 synthase activity can inhibit the differentiation of CD4 + T cells into Th17 cells (7) and reduce cytokine production in activated T cells during viral infection (31).…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…The essential proximal TCR signaling molecules LCK and LAT reside in different lipid raft subsets that fuse upon TCR stimulation (33), and the interaction of TCR-associated signaling molecules (including LCK, LFA1, and PI3K) with GM3 or GM1 induces differential recruitment of downstream signaling targets that affect T cell function (34,35). Moreover, recent reports show that CD4 + and CD8 + T cells exclusively require a-series and o-series GSLs, respectively, for TCR-mediated activation (8,36). The reduction of cellular GSL levels by pharmacological means or by disruption of GM3 synthase activity can inhibit the differentiation of CD4 + T cells into Th17 cells (7) and reduce cytokine production in activated T cells during viral infection (31).…”
Section: Discussionmentioning
confidence: 99%
“…GSLs are enriched predominantly in lipid rafts, regions in the plasma membrane that coordinate the interaction of key signaling molecules that facilitate lymphocyte activation and function (2,5). Furthermore, differential GSL expression influences a range of T cell functions including TCR-mediated signaling (6)(7)(8), apoptosis (9), and recycling and endocytosis of membrane signaling and receptor molecules (4).…”
Section: Introductionmentioning
confidence: 99%
“…3). CTB shows high affinity and specificity for GM1, recognizing the I 3 -sialosylgangliotriaose moiety, Gal␤1,3GalNAc␤1,4(Sia␣2,3) Gal␤1 (43,44). In preliminary studies, Wa infectivity was inhibited to the same extent (48% Ϯ 3%) by CTB at 10 g/ml as at 1 g/ml (Fig.…”
Section: Resultsmentioning
confidence: 82%
“…Although reduced by cellular CTB treatment, Wa infectivity in untreated cells is not inhibited by Neu5Ac␣2Me. This may be because Neu5Ac␣2Me can only compete with VP8* binding to GM1 via the internal Sia, whereas CTB has an extensive a-GM1 binding footprint [the I 3 -sialosylgangliotriaose moiety, Gal␤1,3GalNAc␤1,4(Sia␣2,3)Gal␤1], and high (sub-M) GM1 affinity (43,44). The possibility also exists that Wa preferentially uses alternative receptors on untreated cells, such as the ␣2␤1 integrin, in a manner that is unaffected by Neu5Ac␣2Me competition.…”
mentioning
confidence: 99%
“…Существенную роль в развитии аллергии игра-ют нарушения активности различных субпопуля-ций и апоптоза лимфоцитов [1][2][3], которые могут быть исследованы с помощью оценки ýкспрессии отдельных функциональных молекул на поверх-ности лимфоцитов. Для аллергологии концеп-ция персонализированного подхода на основе трансляционной медицины наиболее ýффектив-но может быть реализована при изучении таких заболеваний, как поллиноз, бронхиальная астма, атопический дерматит.…”
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