ST6Gal I promotes rapid IL-2Rα expression and early proliferation of terminal effector CD8 T cells (46.8)

Abstract ST6Gal I is a glycosyltransferase highly expressed by lymphocytes and cancer cells that catalyzes the addition of α2,6 sialic acid to galactose (Siaα2-6Gal) on N-linked glycoproteins. We discovered that ST6Gal I shows dramatic changes in gene expression during memory CD8 T cell differentiation that corresponds with lectin binding, but the significance of this regulated carbohydrate modification remained a mystery. To identify the significance of these regulated glyco-phenotypic changes, we infected ST6Gal I-/- mice and found that viral-specific cell expansion was impaired. Moreover, defective viral-specific CD8 T cell expansion was due to early intrinsic defects in proliferation of terminal effector cells, whereas memory precursor development was enhanced. We provide direct evidence that loss of ST6Gal I expression by CD8 T cells resulted in delayed surface expression of IL-2Rα in vivo due to impaired IL-2/IL-2R signaling. These results suggest that CD8 T cells regulate ST6Gal I expression to promote proliferation induced by cytokine-dependent signaling.