Official websites use. Share sensitive information only on official, secure websites. Correspondence: michal. Bassani chuv.
Hypochlorous acid HOCl -treated whole tumor cell lysates Ox-L have been shown to be more immunogenic when used as an antigen source for therapeutic dendritic cell DC -based vaccines, improving downstream immune responses both in vitro and in vivo. However, the mechanisms behind the improved immunogenicity are still elusive. To address this question, we conducted a proteomic and immunopeptidomics analyses to map modifications and alterations introduced by HOCl treatment using a human melanoma cell line as a model system.
First, we show that one-hour HOCl incubation readily induces extensive protein oxidation, mitochondrial biogenesis, and increased expression of chaperones and antioxidant proteins, all features indicative of an activation of oxidative stress-response pathways. We found that HLA-II ligands uniquely presented by DCs loaded with Ox-L were more solvent exposed in the structures of their source proteins, contrary to what has been hypothesized so far.
Hence, these results suggest that the increased immunogenicity of Ox-L is, at least in part, due to qualitative and quantitative changes in the HLA-II ligandome, potentially leading to an increased HLA-II dependent stimulation of the T cell compartment i. These results further contribute to the development of more effective and immunogenic DC-based vaccines and to the molecular understanding of the mechanism behind HOCl adjuvant properties.
Keywords: dendritic cells, cancer vaccines, immunotherapy, proteomics, immunopeptidomics. Dendritic cells DCs are professional antigen-presenting cells APCs that play a crucial role at the interface between innate and adaptive immune system [ 1 ]. Their main function is to uptake and process foreign antigens and present them to T cell compartments, thus activating a subsequent immune response against pathogens.
