Autoantigenicity of Ro/SSA antigen is related to a nucleocapsid protein of vesicular stomatitis virus

The fine specificity of a reference human anti-Ro/SSA autoantibody-containing serum has been analyzed by using sequential overlapping octapeptides from the human 60-kDa Ro/SSA antigen. From preliminary data, the most antigenic octapeptide in the carboxyl-terminal 120 amino acid residues of Ro/SSA shares seven of eight Amino acids with the nucleocapsid (N) protein from the Indiana serotype of vesicular stomatitis virus. A sequence comparison of Ro/SSA and N has unexpectedly revealed six small peptides shared by Ro/SSA and N. Fine specificity analysis with 531 octapeptides from the Ro/SSA sequence demonstrates that five of the six shared small peptides are bound by anti-Ro/SSA (P = 0.00017). A more powerful association is not present in 12,476 protein sequences similarly evaluated. In addition, the inclusion of single-residue gaps in Ro/SSA enlarges the sequence similarity of Ro/SSA and N for three of the five small shared antigenic peptides. This additional level of sequence similarity between Ro/SSA and N is unlikely to be the result of chance (P less than 0.0002). While a number of models may explain these data, including independent immune responses to N and Ro/SSA, these results are also consistent with anti-Ro/SSA autoantibodies being the consequence of a specific viral exposure.