BASIC-AMINO-ACIDS PREDOMINATE IN THE SEQUENTIAL AUTOANTIGENIC DETERMINANTS OF THE SMALL NUCLEAR 70K RIBONUCLEOPROTEIN

Autoantibodies binding the 70K nRNP polypeptide are commonly found in the serum of patients with systemic lupus erythematosus. IgG antibodie s binding overlapping octapeptides of 70K nRNP have been evaluated in 10 patients with anti-nRNP precipitins, seven patients with other auto immune serology, and four normal human sera. Neither normal controls n or patients without an anti-nRNP precipitin significantly bind any of the 70K nRNP octapeptides. Sera containing an anti-nRNP precipitin str ongly bind various combinations of eleven different regions of the 70K nRNP protein. One antigenic region is consistently the most reactive in nine of ten nRNP precipitin positive sera tested. This sequence, KD KDRDRKRRSSRSR, is highly charged and has a similar pattern of alternat ing basic amino acids also present in seven of the other purported hum oral autoimmune epitopes of the 70K nRNP polypeptide. The closely rela ted DRKR and ERKR are important components of two of these epitopes. A ll regions of the 70K peptide bound by human anti-nRNP precipitin posi tive sera are very rich in the basic amino acids, especially lysine (c hi-square = 23.03, odds ratio = 13.3, P < 0.000001).