SEQUENTIAL AUTOANTIGENIC DETERMINANTS OF THE SMALL NUCLEAR RIBONUCLEOPROTEIN SM-D SHARED BY HUMAN LUPUS AUTOANTIBODIES AND MRL LPR LPR ANTIBODIES/

Autoantibodies directed against the Sm proteins of the spliceosome com plex are found in approximately 25% of systemic lupus erythematosus (S LE) patient sera. To determine which regions of the Sm D polypeptide a re involved in the lupus autoimmune response, binding to overlapping o ctapeptides of Sm D has been evaluated with sera from nine Sm D-positi ve patients, six patients with other autoimmune serology, and five nor mal human sera. Lupus patient sera which are Sm precipitin-positive bi nd various combinations of five regions of the peptide. The major anti genic region, Epitope 5 (REAVA(GR)(10)GGPRR), is bound by eight of nin e Sm precipitin-positive sera tested. This region of Sm D shows signif icant sequence homology with Epstein-Barr nuclear antigen-1. To determ ine the fine specificity of the murine Sm response, four unique Sm D M oAbs derived from MRL lpr/lpr mice and three adult anti-Sm-positive MR L lpr/lpr mouse sera have been analysed. Two of these monoclonals, KSm 4 and Y12, as well as the MRL lpr/lpr sera tested, show binding with Epitope 5. Another of these monoclonals, KSm 2, binds octapeptides 84- 98, DVEPKVKSKKREAVAG, which corresponds to Epitope 4 of this study. An tibodies from SLE patients with autoimmune serology other than anti-Sm bind the carboxyl glycine-arginine repeat (GR)lo peptides of Sm D. Ho wever, none of the antibodies tested from patients who do not have lup us and who have different autoimmune serology binds any of the Sm D oc tapeptides. Normal controls did not significantly bind any of the Sm D octapeptides. These results describe two major regions of shared anti genicity of Sm D between sera from SLE patients and MRL lpr/lpr mice, thereby establishing a basis for the cross-species similarity of autoi mmunity to the Sm autoantigen in SLE.