A peptide based on the sequence of the CDR3 of a murine anti-DNA mAb is a better modulator of experimental SLE than its single amino acid-substituted analogs.
A peptide based on the complementarity determining region (CDR) 3 of a pathogenic anti-DNA 16/6 Id(+) monoclonal antibody was previously shown to be a dominant T-cell epitope in experimental SLE, and to be capable of inhibiting SLE-associated proliferative responses. Single amino acid-substituted analogs of pCDR3 were designed and analyzed for their ability to stimulate or inhibit the proliferation of a pCDR3-specific T-cell line. Alterations in positions 9 and 10 neutralized the proliferative potential of pCDR3, whereas alterations in positions 6-8 and 11-15 retained the proliferative potential of the peptides. Similar to pCDR3, its analogs Ala11 and Nle13 inhibited efficiently the in vivo priming of lymph node cells either to pCDR3 or to the human monoclonal anti-DNA 16/6 Id(+) antibody. Substituting both positions 11 (Tyr --> Ala) and 13 (Met --> Nle) reduced this inhibitory capacity compared to the single substituted analogs. Also, truncation of pCDR3 at the C- and/or N-terminus obliterated the inhibitory activities of the peptide. Analogs Ala11 and Nle13 immunomodulated serological and clinical smanifestations of experimental SLE. Nevertheless, the original pCDR3 was a more efficient modulator of the disease.
Brosh
N
N
Department of Immunology, The Weizmann Institute of Science, Rehovot, 76100, Israel.
Zinger
H
H
Fridkin
M
M
Mozes
E
E
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000276:immunology*; D004247:DNA / Q000276:immunology*; D005260:Female; D007130:Immunoglobulin Idiotypes; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced* / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D022801:Complementarity Determining Regions; D007130:Immunoglobulin Idiotypes; D010455:Peptides; D004247:DNA