Galectin-8 enhances antigen uptake, processing and presentation to CD4+ T cells

PRATO CECILIA A.; TRIBULATTI MARIA V.; CARABELLI JULIETA; CAMPETELLA OSCAR

BUENOS AIRES

Simposio; 3rd Argentinean Symposium on Glycobiology; 2019

Galectin-8 (Gal-8) is a mammalian lectin endowed with pro-inflammatory properties. Our recent findings showed that Gal-8 has the ability to activate dendritic cells (DC) by inducing the expression of costimulatory molecules, the secretion of pro-inflammatory cytokines, and an augmented capacity of antigen-specific T cell stimulation. We also found that Gal-8 improves the specific and neutralizing humoral response in the Foot-and-Mouth Disease virus experimental model, resulting in animal protection upon viral challenge. Here, we aim to study the molecular mechanism underlying the stimulating effect of Gal-8 in the elicitation of the immune response. First, we observed that Gal-8 not only binds to DC surface on a lectin dependent manner, but it also induces the pre-attachment of soluble and particulated antigens, resulting in a more efficient internalization. By confocal microscopy, we observed that Gal-8 is endocytosed together with OVA antigen, finding a significant co-localization with EEA1 and transferrin, but not with Lamp1 positive-compartments. In addition, using DQ-OVA (a fluorogenic substrate for lysosomal proteases), we found that antigen processing is also enhanced in the presence of Gal-8. Finally, we observed a significant increment of specific CD4+T cell proliferation when cultured with DC previously pulsed with OVA and Gal-8, supporting the notion that Gal-8, by promoting antigen uptake and processing, enhances its presentation to T cells.