Gangliosides are major components of highly organized membrane microdomains or rafts, yet little is known about the role of gangliosides in raft organization. This is also the case of gangliosides in T cell development and activation. Primary CD4
+ T cells and CD8
+ T cells preferentially express differential series of gangliosides: the former a-series and the later o-series. Consistent with this, a-series and o-series ganglioside deficiency results in CD4
+ and CD8
+ T cell dysfunction, respectively. Ganglioside GM3 synthase deficiency, which leads to the lack of a-series gangliosides, ameliorates CD4
+ T cell-mediated airway hypersensitivity in a mouse model of allergic asthma. It is therefore suggested that a variety of rafts with different gangliosides are formed on the plasma membrane of CD4
+ and CD8
+ T cells, which defines the immune function of individual T cell subsets. This review focuses on the selective role of different gangliosides expressed in individual T cell subsets.
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