A peptide based on the CDR1 of a pathogenic anti-DNA antibody is more efficient than its analogs in inhibiting autoreactive T cells

A peptide based on the sequence of the complementarity determining regions 1 (pCDR1) of a pathogenic murine monoclonal anti DNA antibody (5G12) that b ears the 16/6 Id, was synthesized. This peptide was shown to be immunodomin ant in BALB/c mice, and induced a mild lupus-like disease upon immunization . Furthermore, the pCDR1 when injected in a soluble form was capable of inh ibiting the proliferation of lymph node cells primed to either the peptide or the anti-DNA, 16/6 Id antibodies of either murine (5G12)or human (16/6 I d) origin. We have designed and synthesized 39 analogs based on pCDR1 with single amino acid substitutions. Out of the above, two analogs, namely, Asp 14 and Ser16 inhibited the proliferative responses of a pCDR1-specific T ce ll line to its stimulating peptide by more than 50%. These two analogs were therefore further studied. Administration of analog Ser16 concomitant with the immunization with pCDR1 inhibited efficiently the proliferative respon ses of lymph node cells to pCDR1, although pCDR1 was more efficient in its inhibitory capacity. Neither of the analogs were capable of inhibiting sign ificantly the proliferative responses to the human monoclonal anti-DNA anti body with the 16/6 Id whereas pCDR1 did so efficiently. Thus, pCDR1 is more efficient than all its tested analogs in immunomodulating SLE associated i mmune responses.