[Correction added after online publication May 15, 2012: Article title has been corrected.]
Beyond glycoproteins as galectin counterreceptors: tumor-effector T cell growth control via ganglioside GM1
Article first published online: 23 APR 2012
© 2012 New York Academy of Sciences.
Annals of the New York Academy of Sciences
Volume 1253, Glycobiology of the Immune Response pages 206–221, April 2012
How to Cite
Ledeen, R. W., Wu, G., André, S., Bleich, D., Huet, G., Kaltner, H., Kopitz, J. and Gabius, H.-J. (2012), Beyond glycoproteins as galectin counterreceptors: tumor-effector T cell growth control via ganglioside GM1. Annals of the New York Academy of Sciences, 1253: 206–221. doi: 10.1111/j.1749-6632.2012.06479.x
- Issue published online: 23 APR 2012
- Article first published online: 23 APR 2012
- GM1 ganglioside;
- immune suppression;
- T cells
Glycoprotein glycan chains, by virtue of structure, topology of presentation and connection to signal-inducing units, are functional galectin counterreceptors. As example, cross-linking of the α5β1 integrin by galectin-1 on carcinoma cells leads to G1 arrest or anoikis. Contact-dependent switching from proliferation to differentiation in cultured neuroblastoma cells (SK-N-MC) also utilizes galectin-1. Activity enhancement of a cell surface sialidase underlies the shift in glycan display to ganglioside GM1. Its pentasaccharide within microdomains becomes the target. Similarly, this recognition pair is upregulated upon T cell activation. Cross-linking of GM1 along with associated α4/α5β1 integrins elicits Ca2+-influx via TRPC5 channels as the relevant response for T effector cell (Teff) suppression. Unlike Teff cells from wild-type mice, those from genetically altered mice lacking GM1 are not suppressed by galectin-1 or regulatory T cells. Similarly, in the context of GM1 deficiency in NOD mice, Teff cells are associated with resistance to regulatory T cell suppression, which is reversed by applied GM1. The broad array of glycosphingolipid structures suggests the possible existence of several novel counterreceptors targeted to endogenous lectins, with sulfatide–galectin-4 interplay within apical delivery serving as recent example.