The presence of circulating antibodies directed against nuclear antigens is a common symptom to many systemic rheumatic diseases. Many patients with systemic lupus erythematosus (SLE) produce antibodies which interact with abundant small nuclear ribonucleoprotein complexes (snRNPs) found in eukaryotic cells. The class of autoimmune sera which precipitate snRNPs containing the small nuclear RNAs U1, U2, U4, U5 and U6 is called anti-Sm. Since anti-Sm antibodies are only rarely produced by patients with other connective tissue diseases, the presence of this specificity serves as a useful serological marker for SLE. One of the proteins recognized by anti-Sm sera is the 11,000 dalton "E" protein. This protein is a component of all of the anti- Sm reactive snRNPs, but little is known about its structure or function. We plan to use our recently isolated cDNA clone for the E protein to characterize the genes for this autoimmune antigen, and to investigate the role of this protein in cellular physiology. Finally we plan to exploit the protein structural information obtained from sequencing the E protein gene to determine which portion of this protein is actually recognized by anti-Sm antibodies. These studies should not only enhance our understanding of the etiology of autoimmune disease, but should help us design a rational strategy for the cloning and analysis of related Sm antigens.