International Immunology, Vol. 13, No. 2, 223-232,
February 2001
© 2001 Japanese Society for Immunology
Peptide mimicking antigenic and immunogenic epitope of double-stranded DNA in systemic lupus erythematosus
1 Bioprocessing Technology Centre, and
2 Departments of Medicine and
3 Biochemistry, National University of Singapore, Singapore 119260, Republic of Singapore
Correspondence to: Correspondence to: Z.-J. Yao, National Center for Human Genome Research, BDA, #3-707 North Yongchang Road, Beijing 100176, China
Autoantibodies to double-stranded (ds) DNA are an important diagnostic marker and pathogenic factor for systemic lupus erythematosus (SLE). Identifying dsDNA mimotopes is a way to discover diagnostic and therapeutic candidates for SLE. `Mono-specific' SLE anti-dsDNA antibodies were obtained by affinity purification using dsDNA-coupled Sepharose column. Using the anti-dsDNA antibodies to screen a phage peptide library, we were able to identify a mimotope that has a motif peptide sequence of RLTSSLRYNP. This chemically synthesized peptide could be recognized by 88% (37 out of 42) of anti-dsDNA antibody-positive SLE sera with a cut-off point at mean + 3 SD of the negative control sera at OD492. The reaction of the peptide with SLE sera in ELISA was highly correlated with that of dsDNA (r = 0.809, P < 0.0001). Of particular interest, not only dsDNA but also single-stranded (ss) DNA and native RNA could inhibit the binding of the peptide with SLE sera, suggesting that the mimotope is shared by ds and ssDNAs as well as native RNA, whereas denatured RNA was not observed to inhibit the binding. The peptide was also able to elicit an immune response in rabbits and the anti-peptide rabbit serum was observed to cross-react with the peptide, ss and dsDNAs, and ss and dsDNAs could inhibit the binding of the anti-peptide serum and the peptide. However, the inhibition was not obtained with RNA. Our findings demonstrate the potential of the peptide mimic in diagnostic tests of SLE, and in the investigation of anti-DNA antibody origin and of DNA–anti-DNA antibody interaction.
Keywords: autoantibody, anti-double-stranded DNA antibody, mimotope, phage peptide library
4 Present address: Institute of Dermatology, National Skin Centre, 1 Mandalay Road, Singapore 308205, Republic of Singapore
5 Present address: National Center for Human Genome Research, BDA, #3-707 North Yongchang Road, Beijing 100176, China
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