IMMUNIZATION WITH VESICULAR STOMATITIS-VIRUS NUCLEOCAPSID PROTEIN INDUCES AUTOANTIBODIES TO THE 60-KD RO RIBONUCLEOPROTEIN PARTICLE

Background: Systemic lupus erythematosus (SLE) is an autoimmune disord er of unknown etiology that is characterized by antibodies binding rib onucleoprotein complexes, The epitopes of SLE associated 60 kd Ro (or SSA) autoantigen share sequence with vesicular stomatitis virus (VSV) nucleocapsid (N) protein and SLE patients with anti-Re are more likely to bind the N-protein than anti-Re negative patients. Method: We immu nized New Zealand white (NZW) rabbits with purified VSV N-protein to e xamine the relationship between the immune response to N-protein and a nti-Ro. Results: After multiple immunizations with VSV N-protein, NZW rabbits produced not only IgG antibodies to VSV N-protein but also an autoimmune response to Ro antigen, The IgG fraction of the rabbit immu ne serum precipitates 60 kd Ro protein as well as its associated Y RNA s, Antibodies elicited by 10 immunizations of VSV N-protein bind to at least 20 linear epitope groups on VSV N-protein and over 25 linear ep itope groups on 60 kd Ro protein. These antibodies also bound 5 of the 6 shared sequences between 60 kd Ro protein and VSV N-protein. Conclu sions: Our data demonstrate that an immune response initiated towards a foreign antigen, selected on the basis of sharing short sequence sim ilarity with the autoantigenic epitopes of an autoantigen, can lead to an autoimmune response,