Epitope Regions on UI Small Nuclear RNA Recognized by Anti-U1RNA-specific Autoantibodies

Autoantibodies specifically directed to U1RNA were found in patients suffering from systemic lupus erythematosus (SLE) overlap syndromes. To obtain more insight in the mechanism responsible for this UlRNA-specific antibody formation and to use the antibodies eventually as a tool to study UlRNA-protein (UlRNP) interactions, the B cell epitopes on U1RNA were mapped. Using in vitro synthesized domains of U1RNA, the main epitope regions were found in stemloops II and IV. Fur-thermore, 3'-end or 5'-end truncation of both stemloop II and stemloop IV showed that the conformation of the stemloops is critical for antibody recognition. Mutant studies on both stem-loops indicated that in the case of stemloop II the stem is the main antigenic region, whereas in stemloop IV, the loop (E-loop) is a main target. The results of this study support the idea that the anti-U1RNA autoantibody could be the result of a process driven by the human U1RNP complex itself (antigen