Effect of hypochlorous acid on antigen processing and presentation

Abstract

Dendritic cells play a key role in both innate and adaptive immunity. Recognition and presentation of antigens on the major histocompatibility complex (MHC) provide an efficient response against infections. However, this response strongly depends on antigen presentation. During inflammation several oxidative reactions occur that lead to the production of oxidants. Under these conditions protein antigens are exposed to high concentrations of hypochlorous acid (HOCl) and hydrogen peroxide (H2O2) that conduct changes in antigen structure and enhance the specific T cells response. However, the mechanism of presentation of oxidized antigens is presently unknown. In this thesis, we have focused on the mechanism involved in the enhancement of the T cell response to oxidized proteins. In particular, we have studied the uptake, processing and presentation of oxidized antigens in in vitro and in vivo mice models to MHC II‐restricted T cells; we have investigated the potential receptor‐mediated mechanism underlying the enhanced immunogenicity of oxidized antigens; and finally we have analyzed the connection between protein chemical modifications and the enhanced response to oxidized antigens