Autoantibody of an immortalized human lymphocyte cell line, Su-2E4, derived from peripheral lymphocytes of a patient with mixed connective tissue disease, showed specific binding of the 68K polypeptide of U1 small nuclear RNP (snRNP) and immunoprecipitation of U1 RNA. The reaction patterns of Su-2E4 and a murine monoclonal anti-(U1)snRNP line, 2.73, and results of a competition assay with the 2 antibodies suggest similar, but not necessarily identical, epitope recognition.Autoantibodies to nuclear and cytoplasmic components are frequently found in patients with systemic rheumatic diseases (1-3). The autoantigens are often nucleic acid-associated proteins, such as small nuclear RNP (snRNP) (4). Circulating autoantibodies to some of these antigens are characteristic of Presented by Jintao Chen in partial fulfillment of the requirements for a PhD degree,