Proliferating cell nuclear antigen (PCNA), also known as auxiliary protein of DNA polymerase delta, is involved in DNA replication and repair. Certain patients with systemic lupus erythematosus (lupus) produce autoantibodies to PCNA and the autoantibody-defined epitopes of PCNA have been inferred to be conformation-dependent. Based on antigenic properties of continuous primary structure peptides, compound peptides composed of covalently linked discontinuous sequences were synthesized and used as immunogens in rabbits. One compound peptide induced an antibody response to a nuclear antigen which demonstrated a cell cycle-related pattern of nuclear immunofluorescence with maximum expression in the DNA synthesis phase of the cell cycle associated with other features which simulated the conformation-dependent properties of lupus defined auto-epitopes. Other rabbit antibodies raised against different compound peptides did not show such properties and recognized epitopes which were continuous primary sequence regions. These results show that from analysis of antigenic sites on a protein, it might be possible to construct synthetic compound peptides which can mimic conformation-dependent epitopes recognized by spontaneously occurring autoantibodies.