MODULATION OF MURINE SYSTEMIC LUPUS-ERYTHEMATOSUS WITH PEPTIDES BASEDON COMPLEMENTARITY-DETERMINING REGIONS OF A PATHOGENIC ANTI-DNA MONOCLONAL-ANTIBODY

Experimental systemic lupus erythematosus (SLE) can be induced in naiv e mice by immunization with a murine monoclonal anti-DIVA antibody (mA b), 5G12, that bears a major idiotype designated 16/6 Id. Strain-depen dent differences were observed in the proliferative responses of lymph node cells of mice immunized with two peptides based on the sequences of the complementarity determining region (CDR) 1 and 3 of mAb 5G12, The capacity of the peptides to bind to major histocompatibility compl ex class II molecules correlated with the proliferative responses, Imm unization of high responder strains with the CDR-based peptides led to production of autoantibodies and clinical manifestations characterist ic to experimental SLE. The CDR-based peptides could prevent autoantib ody production in neonatal mice that were immunized later either with the peptide or with the pathogenic autoantibody. Furthermore, the pept ides inhibited specific proliferation of lymph node cells of mice immu nized with the same peptide, with mAb 5G12 or with the human mAb anti- DNA, 16/6 Id, Thus, the CDR-based peptides are potential candidates fo r therapy of SLE.