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Publication : The two enantiomers of 2-hydroxyglutarate differentially regulate cytotoxic T cell function.

First Author  Foskolou IP Year  2023
Journal  Cell Rep Volume  42
Issue  9 Pages  113013
PubMed ID  37632752 Mgi Jnum  J:351830
Mgi Id  MGI:7525048 Doi  10.1016/j.celrep.2023.113013
Citation  Foskolou IP, et al. (2023) The two enantiomers of 2-hydroxyglutarate differentially regulate cytotoxic T cell function. Cell Rep 42(9):113013
abstractText  2-Hydroxyglutarate (2HG) is a byproduct of the tricarboxylic acid (TCA) cycle and is readily detected in the tissues of healthy individuals. 2HG is found in two enantiomeric forms: S-2HG and R-2HG. Here, we investigate the differential roles of these two enantiomers in cluster of differentiation (CD)8(+) T cell biology, where we find they have highly divergent effects on proliferation, differentiation, and T cell function. We show here an analysis of structural determinants that likely underlie these differential effects on specific alpha-ketoglutarate (alphaKG)-dependent enzymes. Treatment of CD8(+) T cells with exogenous S-2HG, but not R-2HG, increased CD8(+) T cell fitness in vivo and enhanced anti-tumor activity. These data show that S-2HG and R-2HG should be considered as two distinct and important actors in the regulation of T cell function.
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