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 molecular mimicry is a potential mechanism of autoantibody generation, we aligned the identified variola virus and TRIM epitopes; the sequence annotation thresholds that we used in our bioinformatics pipeline guaranteed robust annotation of the epitope sequences. This would affect cross-kingdom epitope alignment, since we have maximized the phylogenetic distance between each microbial epitope and human proteins. To account for this, we started our epitope sequence analysis with the widest possible diversity of identified variola and TRIM epitopes, sacrificing specificity i.e. epitopes with more than 80% match to variola virus, and TRIM epitopes with an identity of more than 50%. The phylogenetic distances are shown in the circular cladogram in Figure 6 . We identified two different clades containing leaf nodes of TRIM and variola epitopes of high similarity (branch lengths <0.1). The first clade involved the TRIM3 epitope "RIPDDVRRRPGC" and three additional epitopes The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.25.007534 doi: bioRxiv preprint protein product and viral DNA polymerase processivity factor). We reinstated the annotation specificity thresholds for TRIM and variola epitopes to the default levels (strict, high specificity, maximisation of phylogenetic distances) ( Figure S7A ). The epitope sequence "RI(P)DDVRRRPGC" was retained and shared between TRIM3 (branch length: 0.0541) and VARV GER58 hdlg 202 (branch length: 0.0344). The epitope sequences "SSHARYKSLRFS" and "SSHARYKSLRF" were specific for variola virus but were no longer annotated as TRIM epitopes ( Figure S7A ). We asked whether the above epitope sequences are shared amongst different Poxviridae species that we identified in DM P20