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.
Scofield
R H
RH
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
Harley
J B
JB
D000595:Amino Acid Sequence; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D002213:Capsid / Q000276:immunology*; D003429:Cross Reactions; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*; D000099207:SS-A Antigen
D001323:Autoantibodies; D001324:Autoantigens; D010455:Peptides; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D014758:Viral Core Proteins; D000099207:SS-A Antigen; C116006:RO60 protein, human