ST6Gal‐I gene expression is required for optimal Ag‐specific CD8 T cell expansion in vivo

Glycosylation can affect the localization and interactions of cell surface glycoproteins, impacting cell signaling and function. ST6Gal‐I is a glycosyltransferase expressed by T and B cells that catalyzes the addition of a2,6 sialic acid to galactose on N‐linked glycoproteins such as CD45. We show that changes in expression of ST6Gal‐I during memory CD8 T cell differentiation results in changes in cell surface sialylation as demonstrated by SNA lectin binding. Moreover, lectin binding revealed heterogeneity within the memory CD8 T cell population isolated from tissues, identifying SNAhigh and SNAlow memory CD8 T cells. To further understand the role of this modification in T cell function in vivo, we examined ST6Gal‐I null mice following LCMV infection. Our analysis revealed lower numbers of Ag‐specific CD8 T cells at day 8 post‐infection compared to WT mice. In addition, adoptive transfer of P14×ST6Gal‐I+/− or P14×ST6Gal‐I−/− cells into WT recipient mice show reduced numbers of transgenic null CD8 T cells on day 8, suggesting the defect is T cell intrinsic. Finally we demonstrate using in vivo CFSE labelling of purified P14×ST6Gal‐I+/− or P14×ST6Gal‐I−/− CD8 T cells into WT recipient mice that null transgenic CD8 T cells show substantially reduced proliferation. These studies suggest that differential expression of surface carbohydrates can significantly impair CD8 T cell activation and proliferation in vivo.