A common autoepitope near the carboxyl terminus of the 60-kD Ro ribonucleoprotein: sequence similarity with a viral protein.
The Ro ribonucleoprotein is composed of hY RNA and a 60.7-kD peptide that is antigenic for autoantibodies produced by many patients with systemic lupus erythematosus or Sjögren's syndrome and mothers of newborns with complete congenital heart block. A major immunoreactive fragment (13 kD) of the 60-kD Ro is bound by 28 of 45 (62%) of the anti-Ro sera tested. Amino acid sequence analysis localizes this fragment to the carboxyl end of the 60-kD Ro peptide. All possible overlapping octapeptides of this 13-kD peptide of 60-kD Ro have been assessed for antigenicity. Sera that bind the 13-kD peptide fragment in immunoblot generally also bind the octapeptides of Ro spanning the sequence AIALREYRKKMDIPA (P less than 0.01). Inhibition studies with synthetic peptides and purified Ro have established specificity for reference serum antibody binding to an antigenic octapeptide, EYRKKMDI, from this region. The closely related sequence EYRKKLMD is found in the nucleocapsid protein of vesicular stomatitis virus and may portend an immunologic link to this or a related viral antigen. These results also demonstrate that despite fine specificity variation between human sera, there are recurring patterns of anti-Ro binding shared by some patients who have precipitating anti-Ro autoantibodies.
Scofield
R H
RH
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
Dickey
W D
WD
Jackson
K W
KW
James
J A
JA
Harley
J B
JB
D000595:Amino Acid Sequence; D001324:Autoantigens / Q000737:chemistry*; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins / Q000737:chemistry* / Q000276:immunology*; D012689:Sequence Homology, Nucleic Acid; D014721:Vesicular stomatitis Indiana virus / Q000737:chemistry / Q000276:immunology; D014764:Viral Proteins / Q000737:chemistry* / Q000276:immunology*; D000099207:SS-A Antigen
D001324:Autoantigens; D000939:Epitopes; D010446:Peptide Fragments; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D014764:Viral Proteins; D000099207:SS-A Antigen; C116006:RO60 protein, human