Expanded presentation of Lyme autoantigens and identification of a novel immunogenic CD4+ T cell epitope from <i>Borrelia burgdorferi</i>MCP4 in murine Lyme arthritis

Abstract Lyme arthritis (LA), caused by Borrelia burgdorferi (Bb), is often accompanied autoimmune T and B cell responses, but the mechanisms of infection-induced autoimmunity are unclear. We used an immunopeptidomics approach to identify potential autoantigens immunogenic Bb antigens, which were validated histology testing reactivity. C57BL/6 (B6) mice, develop mild inflammatory LA, B6 Il10−/− (IL10 KO) severe, persistent infected with for 4 or 16 weeks, MHCII-bound peptides from inguinal popliteal lymph nodes identified LC-MS/MS. Joint inflammation, fibrosis, vascular remodeling analyzed H&amp;E, Masson’s trichrome, anti-CD31 immunohistochemistry, respectively. Six LC-MS/MS, one epitope methyl-accepting chemotaxis protein (MCP4) was CD4+ antigen. Over 10,000 self peptides, particularly proteins involved in cholesterol metabolism, tissue damage, inflammation mice. Presentation previously human apolipoprotein B-100, fibronectin, type V collagen expanded suggestive spreading. Consistent data, joints showed increased infiltrate, fibrosis neovascularization compared uninfected In conclusion, this revealed key insights into LA indentified a novel antigen MCP4. Supported grants NIAID (R21AI148982)