Autoepitopes of the 52-kd SS-A/Ro molecule.
OBJECTIVE
This study was undertaken to clarify the mechanisms responsible for the generation of anti-52-kd SS-A/Ro autoantibodies and to elucidate why, as has recently been reported, anti-52-kd autoantibodies preferentially recognize the denatured form rather than the native 52-kd molecule.


METHODS
Using a series of truncated 52-kd autoantigens, produced as beta-galactosidase fusion proteins in Escherichia coli, the B cell epitope distribution was probed with 18 anti-Ro-positive sera by immunoblotting and by enzyme-linked immunosorbent assay.


RESULTS
Nearly all the antigenicity of the molecule was found to be linked to its leucine zipper region. In a further study using 9 of the 18 sera, the antigenicity of the molecule was found to be mainly formed by multiple conformational epitopes, and one of these epitopes appeared to be universally recognized by all the sera tested.


CONCLUSIONS
The recognition of multiple epitopes indicates that the Ro 52-kd antigen itself drives the autoimmunity to this molecule. Further, the concentration of the antigenicity at the leucine zipper region may explain why anti-52-kd antibodies preferentially recognize the denatured protein rather than its native form.
Kato
T
T
Institute of Medical Science, St. Marianna University School of Medicine, Kanagawa, Japan.
Sasakawa
H
H
Suzuki
S
S
Shirako
M
M
Tashiro
F
F
Nishioka
K
K
Yamamoto
K
K
D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D004247:DNA / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D016350:Leucine Zippers; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D020733:RNA, Small Cytoplasmic; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology; D012261:Ribonucleoproteins / Q000235:genetics / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000097:blood / Q000276:immunology; D000099207:SS-A Antigen
D001323:Autoantibodies; D001324:Autoantigens; D004247:DNA; D017931:DNA Primers; D000939:Epitopes; D020733:RNA, Small Cytoplasmic; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C116006:RO60 protein, human