A Peptide Based on the CDR1 of a Pathogenic anti-DNA Antibody is more Efficient than its Analogs in Inhibiting Autoreactive T Cells

• Published in: Immunobiology (1979) 2000-11, Vol.202 (4), p.383-393
• Main Authors: Eilat, Eran, Fridkin, Mati, Mozes, Edna
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino Acid Substitution; Animals; anti-DNA antibodies; Antibodies, Antinuclear - immunology; Antibodies, Monoclonal - immunology; Cell Division; Cell Line; Complementarity Determining Regions - immunology; complementarity-determining region 1; Female; Humans; Lupus Erythematosus, Systemic; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Peptides - chemical synthesis; Peptides - immunology; T-Lymphocytes - immunology
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/S0171-2985(00)80041-8

A peptide based on the sequence of the complementarity determining regions 1 (pCDR1) of a pathogenic murine monoclonal anti-DNA antibody (5G 12) that bears the 16/6 Id, was synthesizedThis peptide was shown to be immunodominant in BALB/c mice, and induced a mild lupus-like disease upon immunizationFurthermore, the pCDR1 when injected in a soluble form was capable of inhibiting the proliferation of lymph node cells primed to either the peptide or the anti-DNA, 16/6 Id antibodies of either murine (5G 12) or human (16/6 Id) originWe have designed and synthesized 39 analogs based on pCDR1 with single amino acid substitutionsOut of the above, two analogs, namely, Asp 14 and Ser16 inhibited the proliferative responses of a pCDR1-specific T cell line to its stimulating peptide by more than 50%These two analogs were therefore further studiedAdministration of analog Ser16 concomitant with the immunization with pCDR1 inhibited efficiently the proliferative responses of lymph node cells to pCDR1, although pCDR1 was more efficient in its inhibitory capacityNeither of the analogs were capable of inhibiting significantly the proliferative responses to the human monoclonal antiDNA antibody with the 16/6 Id whereas pCDR1 did so efficientlyThus, pCDR1 is more efficient than all its tested analogs in immunomodulating SLE associated immune responses.