EPSTEIN-BARR VIRUS-INDUCED AUTOIMMUNE RESPONSES .2. IMMUNOGLOBULIN-G AUTOANTIBODIES TO MIMICKING AND NONMIMICKING EPITOPES - PRESENCE IN AUTOIMMUNE-DISEASE

During infectious mononucleosis, IgM autoantibodies are generated to a protein, p542, which contains a glycine-rich 28-mer epitope cross-rea ctive with the Epstein-Barr nuclear antigen-1 through Epstein-Barr nuc lear antigen-1's glycine/alanine repeat. In normal individuals it is u ncommon to find IgG anti-p542, but among patients with progressive sys temic sclerosis, systemic lupus erythematosus, and ulcerative colitis high IgG anti-p542 (>3 SD above the mean of normal 20-50 yr controls) occurred frequently. Lesser elevations occurred in Sjogren's syndrome, rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease, bu t none with chronic hepatitis B infection. The reactive epitopes on p5 42 were mapped with deletion mutants, which indicated that the glycine -rich 28-mer was the major antigenic determinant, with lesser antibody responses to other epitopes. We conclude that normally there is an in ability to generate IgG autoantibodies to the cross-reactive (mimickin g) epitope of the p542 host protein, but that this inability is overco me in a proportion of patients with autoimmune disease. We conclude al so that non-cross-reactive autoepitopes exist on p542 protein, to whic h IgG autoantibodies can commonly be formed in autoimmune disorders. T he mechanisms responsible for the latter must involve different mechan isms than those responsible for autoantibodies to the mimicking epitop e.