B-CELL EPITOPE ON THE U1 SNRNP-C AUTOANTIGEN CONTAINS A SEQUENCE SIMILAR TO THAT OF THE HERPES-SIMPLEX VIRUS PROTEIN

The mechanism of autoantibody production in autoimmune diseases is not well understood. In the present study we performed the B cell epitope mapping of the U1 small nuclear ribonucleoprotein (snRNP)-C, one of t he target molecules of anti-nRNP autoantibody to investigate how B cel ls respond to the autoantigen. After cloning and expression of a full length complementary DNA (cDNA) encoding the U1-C protein, several tru ncated mutants of the cDNA were constructed and expressed in E. coli. Although a few epitopes were distributed on the whole molecule, all an ti-C protein antibody-positive patients' sera tested recognized the re gion between amino acid residues 102 and 125 of the coding sequence. T his universal epitope region contains an amino acid sequence similar t o that of the herpes simplex virus type 1 ICP4 protein. The peptides r epresenting each molecule were cross-reactive to each other. In additi on this region cross-reacted to the B/B' protein. These observations s uggest that molecular mimicry might be involved in the initiation of a utoantibody production, followed by cross-reactive events between the autoantigens and by antigen-driven mechanisms to generate more complic ated autoantibody patterns against the U1 snRNP complexes.