IL-2 linked to a peptide from influenza hemagglutinin enhances T cell activation by affecting the antigen-presentation function of bone marrow-derived dendritic cells

Chimeric proteins containing antigen linked to cytokines have shown some pr omise as vaccine candidates but little is known of their mechanism of actio n, particularly at the level of the antigen-presenting cell. We have invest igated this using a chimeric protein in which an immunodominant T cell epit ope from influenza hemagglutinin peptide (HA), recognized in the context of I-E-d, was fused to IL-2, Immature murine dendritic cells (DC) derived fro m bone marrow (BMDC) were used to present the chimeric protein to a T cell hybridoma with TCR specific for the HA peptide (A5 cell line). HA-IL-2 was found to induce significantly higher T cell activation than HA alone. Altho ugh the inclusion of IL-2 and HA separately did increase the response of A5 cells compared to HA alone, they were not as effective as the HA-IL-2 chim eric protein. When an antibody known to block IL-2 receptor cc chain (CD25) was included, A5 activation was reduced, suggesting a role for the recepto r in this process. Expression of CD25 on A5 cells was low during activation , implying that the effect was mediated by CD25+ BMDC, Antigen uptake and p rocessing of HA-IL-2 by BMDC was required since fixing BMDC, prior to antig en exposure, greatly reduced their ability to activate A5 cells. The functi on of CD25 on DC is currently unknown. Our results suggest this receptor ma y play a role in antigen uptake and subsequent T cell activation by recepto r-mediated endocytosis of antigen attached to IL-2. This finding that may h ave implications for the development of a new generation of vaccines.