Epitope mapping of human centromere autoantigen centromere protein C (CENP-C); heterogeneity of anti-CENP-C response in rheumatic diseases.
OBJECTIVE
To analyze the autoantigenic epitopes of centromere protein C (CENP-C) recognized by anti-centromere antibodies (ACA).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Sugimoto
K
K
Department of Applied Biochemistry, Research Institute for Advanced Science and Technology, University of Osaka Prefecture, Japan.
Kuriyama
K
K
Himeno
M
M
Muro
Y
Y
D001324:Autoantigens / Q000276:immunology; D002503:Centromere / Q000276:immunology*; D002868:Chromosomal Proteins, Non-Histone / Q000276:immunology* / Q000378:metabolism; D018604:Epitope Mapping; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008137:Longitudinal Studies; D011487:Protein Conformation; D012216:Rheumatic Diseases / Q000276:immunology* / Q000378:metabolism
D001324:Autoantigens; D002868:Chromosomal Proteins, Non-Histone; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C060905:centromere protein C