The GM2 ganglioside inhibits iNKT cell responses in a CD1d-dependent manner

• Type: Article in International Scientific Journal
• Date: 2018

Authors

Pereira, CS (Author) Other; Ribeiro, H (Author) Other; Perez Cabezas, B (Author) Other; Cardoso, MT (Author) Other; Alegrete, N (Author) Other; Gaspar, A (Author) Other; Leao Teles, E (Author) Other; Macedo, MF (Author) Other

Journal

Title: Molecular Genetics and Metabolism

Vol. 125

Pages: 161-167

ISSN: 1096-7192

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 4 Citations

Scopus - 4 Citations

Other information

Authenticus ID: P-00P-38G

DOI: 10.1016/j.ymgme.2018.07.005

Abstract (EN): Invariant natural killer T (iNKT) cells are a subset of T lymphocytes that recognize lipid antigens presented on Cold molecules at the surface of antigen-presenting cells. GM2 is a glycosphingolipid abundant in cellular membranes and known to bind CD1d molecules, but the functional consequences of this binding are not completely clarified. Herein, we analyzed the effect of GM2 in iNKT cell activation. We found that culturing antigen-presenting cells or total peripheral blood mononuclear cells with GM2 did not induce activation of human iNKT cells, implying that this lipid is not antigenic for human iNKT cells. To investigate if this lipid could inhibit iNKT cell activation, we simultaneously incubated antigen-presenting cells with GM2 and the iNKT cell antigen aGalactosylceramide (a-GalCer) and used them to stimulate iNKT cells. We found that GM2 reduced human iNICf cell activation in a dose-dependent manner. An explanation for this effect could be a direct competition of GM2 with antigenic lipids for CD1d binding. This was demonstrated by the use of an antibody (L363) that stains mouse CD1d:a-GalCer complexes, as in the presence of GM2 the amount of CD1d:a-GalCer complexes are reduced. We further explored the consequences of chronic GM2 overload on human iNKT cells by analyzing iNKT cells in patients diagnosed with GM2 gangliosidoses. We found that pediatric patients present a higher frequency of circulating CD4*- iNKT cells and concomitant lower frequency of CD4-CD8 iNKTs. A lower percentage of iNKT cells expressing the NK marker CD161 was also observed in these patients. In contrast, in two adult patients studied, no differences on iNKT cell phenotype were observed. Altogether, this study uncovers a new role for GM2 in the modulation of iNKT cell activation, thus strengthening the central role of lipid metabolism in iNKT cell biology.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7