UNDERSTANDING THE NUCLEAR LOCALISATION PATTERN AND AUTO IMMUNOGENICITY OF H1 HISTONES

Abstract

Anti-Histone H1 auto antibodies have been characterized as one of the factors that play a role in Systemic Lupus Erythematosus (SLE) disease pathogenesis. However, these studies haven’t considered the presence of different H1 variants. Here, we investigated the auto immunogenic nature of the 6 somatically expressed H1 variants. We found that IgG antibodies from SLE patient sera, recognized multiple epitopes present on all H1 variants. Subsequent studies revealed that, besides being a target of autoantibodies, H1x also contains a region that could activate PBMCs to secrete cytokines. H1x localizes in the nucleolus but H1.5 localizes to the nucleoplasm. To further understand how the apparent pro-inflammatory activity of H1x might affect the immunogenicity of proteins in its proximity, we delineated its molecular context by the Bio-ID method in comparison with H1.5. We identified unique H1x- and H1.5-binding partners. Our results indicated that majority of the H1x-binding partners localized within the nucleolus and some have been previously determined to have auto antigenic properties. In conclusion, our results demonstrate the broad interaction between autoantibodies found in SLE patient sera and H1 histones, with distinct pathogenic properties being attributed to H1x.