Figure 7.

Cellular metabolism affects cellular immunogenicity. A, in addition to affecting MICA expression, glucose, azaserine, and azaserine/hypoxanthine have a similar effect on MICB, ULBP1, ULBP2, and ULBP3. B, AICA-Rs, adenosine, and inosine each induce the expression of ULBP2 and ULBP3 even in 5 mm glucose. As multiple NKG2D ligands are similarly affected, we used anti-NKG2D receptor for blocking assays. C, cells cultured in 25 mm glucose or in 25 mm glucose with azaserine and hypoxanthine were killed more effectively than cells cultured in 5 mm glucose or in 25 mm glucose with azaserine. D, cells cultured in 5 mm glucose with AICA-Rs or adenosine were more susceptible to killing than cells cultured in 5 mm glucose alone. E, similarly, cells cultured in 5 mm glucose with inosine were more susceptible to NK cell cytotoxicity than cells cultured in 5 mm glucose only. F–H, in conditions described in C–E, the addition of a blocking NKG2D antibody prevented a significant amount of induced killing, consistent with an NKG2D-dependent killing mechanism. Error bars, 95% confidence interval.