Microbial and autoantibody immunogenic repertoires in TIF1? autoantibody positive dermatomyositis

Spyridon Megremis; Thomas Walker; Xiaotong He; James O'Sullivan; William E.R. Ollier; Hector Chinoy; Neil Pendleton; Antony Payton; Lynne Hampson; Ian Hampson; Janine Lamb

Since Poxviridae epitopes were enriched in DM, we investigated a potential link between pox viruses and TRIM proteins. We identified epitope sequences with high similarity between TRIM3 and Variola virus in addition to other members of the Poxviridae family. Moreover, TRIM47 had epitopes in common with HIV1 and Synechococcus phage. These high similarity epitopes were identified in the C-terminus of the TRIM proteins; between the filamin and NHL 1 domains for TRIM3, and proximal to the B30.2 domain in TRIM47. The C-terminus of TRIM proteins is under evolutionary positive selection and determines ligand binding specificity, function and subcellular localization; notably the B30.2 domain is associated with ability to restrict viral infection, particularly retroviruses (van Tol et al., 2017) . This finding of high similarity epitope sequences suggests that molecular mimicry, at least amongst specific viral and TRIM epitopes, is a potential mechanism of pathogenesis in DM.