Wnt5A supports antigen cross-presentation and CD8 T cell activation

AbstractAntigen processing, cross-presentation, and antigen-specific CD8 T cell response form part and parcel of T cell-mediated immunity. Yet, lacunae remain in our understanding of antigen processing/presentation and CD8 T cell response. Given the association of Wnt5A signaling with immune homeostasis, we evaluated the utility of Wnt5A in antigen processing, cross-presentation, and CD8 T cell activation. Using mouse bone marrow-derived dendritic cells as antigen-presenting cells and ovalbumin as a model antigen we found that Wnt5A mediated regulation of actin and proteasome dynamics is inherently associated with antigen processing. A Wnt5A-Actin-Protasome axis also contributes to antigen cross-presentation and antigen responsive CD8 T cell expansion. In concurrence with these observations, we demonstrated impaired activation of ovalbumin-specific CD8 T cells in ovalbumin immunized Wnt5A heterozygous mice as illustrated by their poor CD8 T cell recall response to ovalbumin when compared to similarly immunized wild type cohorts. Our results suggest that Wnt5A signaling-directed antigen processing/presentation could be vital for generating CD8 T cell recall response to antigen, thus shedding light on a critical parameter of immunity.