Langerin-mediated internalization of a modified peptide routes antigens to early endosomes and enhances cross-presentation by human Langerhans cells

摘要

The potential of the skin immune system to generate immune responses is well established,and the skin is actively exploited as a vaccination site.Human skin contains several antigen-presenting cell subsets with specialized functions.In particular,the capacity to cross-present exogenous antigens to CD8+ T cells is of interest for the design of effective immunotherapies against viruses or cancer.Here,we show that primary human Langerhans cells (LCs) were able to cross-present a synthetic long peptide (SLP) to CD8+ T cells.In addition,modification of this SLP using antibodies against the receptor langerin,but not dectin-1,further enhanced the cross-presenting capacity of LCs through routing of internalized antigens to less proteolytic early endosome antigen 1+ early endosomes.The potency of LCs to enhance CD8+ T-cell responses could be further increased through activation of LCs with the toll-like receptor 3 ligand polyinosinic:polycytidylic acid (pl:C).Altogether,the data provide evidence that human LCs are able to cross-present antigens after langerin-mediated internalization.Furthermore,the potential for antigen modification to target LCs specifically provides a rationale for generating effective anti-tumor or anti-viral cytotoxic T lymphocyte responses.