To analyze the autoantigenic epitopes of centromere protein C (CENP-C) recognized by anti-centromere antibodies (ACA).
A series of truncated peptides of human CENP-C were expressed in Escherichia coli and immunoblotting analysis was performed with 45 ACA positive sera obtained from patients with different types of autoimmune diseases.
Although 9 epitopes were scattered over the entire molecule, the N terminus was immunodominant for IgG and IgM classes and the C terminus was dominant for IgG class. Both epitopes were separately located within the instability and centromere targeting domains in vivo, or the oligomerization-accessible and homodimerization domains in vitro, respectively. In contrast, minor epitopes were clustered at the internal DNA binding domain. A number of patterns of immunoreactivities against 3 representative antigenic sites by IgG or IgM class antibodies were found.
The results indicated the existence of different anti-CENP-C responses in rheumatic diseases and a possible correlation between antigenic regions and functional sites in the CENP-C antigen.