Vaccine antigen archiving by lymphatic endothelial cells boosts archived antigenspecific CD8 T cell memory responses during a pathogenic challenge

Abstract Numerous studies have shown viral antigens can persist in lymph nodes after the resolution of the infection. We demonstrated that lymphatic endothelial cells (LEC), which comprise the lymphatic vasculature necessary for antigen drainage from the tissue, are the predominant cell type required for the persistence of both vaccine and viral antigens within the lymph node. We termed this process antigen archiving due to the ability of LEC to actively archive antigens to which an immune response has occurred. This process involves antigen acquisition, retention, and exchange of the antigen between LECs and dendritic cells (DC), resulting in the presentation of the archived antigens to archived antigen-specific CD8 memory T cells. In this study, we evaluated the effect of LEC archived antigen on archived antigen-specific memory T cells during a pathogenic challenge. We predicted that a pathogenic challenge would result in the release of the archived antigen and subsequent archived antigen presentation. Following a pathogenic challenge, we found a significant increase in archived antigen-specific endogenous or transferred memory CD8 T cells, compared to bystander activation seen by memory T cells of an unrelated specificity. The phenotype of the archived antigen-specific memory CD8 T cells was more effector-like and led to a significant increase in protection against Listeria monocytogenes (LM)-expressing the archived antigen, in the local area. In conclusion, these findings suggest that archived antigen may be released during a pathogenic challenge. As such, the archived antigen may be acquired by migratory DCs as they traffic through the lymphatics in order to present the archived antigen to memory CD8 T cells acting as an effective boost. NIH R01 AI121209