Efforts toward rational design of Th2-bias immune stimulator through modification on D-Gal-C-4 of α-GalCer derivative
2021
Abstract α-Galactosylceramide (α-GalCer) initiates immune response by activating iNKT cells in a CD1d restricted way. However, its clinical application is quite limited mainly because of the simultaneous secretion of antagonizing Th1- and Th2-type cytokines. With the help of molecular computation, we conducted a rational design of glycolipid to expect a Th2-bias immune response. Accordingly, some of the designed D-galactopyranosyl lipids were synthesized, and their abilities to induce Th2 cytokines through stimulating iNKT cells were investigated both in vitro and in vivo. We found that modification on Gal-C-4 of glycolipids could possibly increase Th2-selecivity, although the cytokine productivity was suppressed ascribing to the weaken interaction of CD1d and TCR in CD1d/glycolipid/TCR triplex.
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