Autoepitopes on autoantigen centromere protein-A (CENP-A) are restricted to the N-terminal region, which has no homology with histone H3

Anti-centromere autoantibodies (ACA) are commonly found in the serum of pat ients with a limited type of scleroderma and other systemic autoimmune dise ases. CENP-A is one of the major antigens against ACA and a histone H3-like protein. To analyse the autoantigenic epitopes of CENP-A, a series of trun cated peptides of human CENP-A were expressed in Escherichia coli and immun oblotting analysis was performed with 91 ACA(+) sera. Eighty sera (88%) wit h the ACA reacted to the 52-amino acids N-terminal region which is not homo logous to H3, while no sera reacted to the C-terminus which has a sequence similarity with H3. Moreover, ELISA was also employed in this study using t wo synthetic peptides corresponding to the amino acid sequences 3-17 (pepti de A) and 25-38 (peptide B). Peptides A and B were reactive to 78 (86%) and 79 (87%) of ACA, respectively. Core antigens of hepatitis B virus (HBV) an d hepatitis C virus (HCV) have similar sequences to peptide A and/or peptid e B, but three sera containing HBV without ACA and five sera containing HCV without ACA were found to be reactive to neither peptide. Centromere local ization of CENP-A is dependent on the H3-like C-terminal domain which is no t autoantigenic, while the antigenic N-terminal domain, which might play un identified functional roles, should be an important region for the inductio n of ACA.