Glycan modification of antigen to enhance Th1 skewing and induction of CD8 T-cells through cross presentation

Antigen uptake by DC and subsequent intracellular routing of antigens is regulated by C-type lectin receptors that recognize glycan structures. Amongst the repertoire of glycans expressed by the widely used model-antigen Ovalbumin (OVA) are mannose structures that target OVA to the Mannose Receptor. We show that modification of antigen with the glycan-structure LewisX re-directs antigen to the C-type lectin MGL1 on Dendritic Cells. LewisX-modified antigen lead to differentiation of CD4+ T-cells towards the Th1-lineage, and enhanced cross-presentation by inducing higher frequencies of antigen-specific CD8+ T-cells. Surprisingly, cross-presentation did not require TLR-signaling, TAP-transporters, nor Cathepsin-S. We conclude that controlled glycosylation of antigens can crucially influence the nature and strength of immune responses and should be considered for optimizing current vaccination strategies. Chapter 3