NATURAL ANTIBODIES THAT REACT WITH V-REGION PEPTIDE EPITOPES OF DNA-BINDING ANTIBODIES ARE MADE BY MICE WITH SYSTEMIC LUPUS-ERYTHEMATOSUS AS DISEASE DEVELOPS

Cross-reactive idiotypes (CRI) have been detected on anti-DNA autoanti bodies associated with lesions typical of systemic lupus erythematosus . In order to analyse the antigenic make up of idiotypes on anti-DNA m onoclonal antibodies (mAb) V-88 (IgG1 kappa) and F-423 (IgG3 kappa), d erived respectively from an adult (NZBxNZW)F-1 and a fetal MRL/Mp-lpr/ lpr mouse, a set of overlapping hexapeptides representing the VH and V L regions of mAb V-88 and F-423 were synthesized and reacted with a ra nge of sera in pepscan enzyme-linked immunosorbent assays (ELISA) take n from normal and lupus mouse strains. Serum pools were collected both from normal BALB/c and lupus MRL/Mp-lpr/lpr and (NZB x NZW)F-1 mice a t 10, 20 and 30 weeks of age and analysed for the presence of spontane ously produced anti-V-region peptide IgM and IgG antibodies. IgM antib odies from both the lupus mice reacted with the same V-region epitopes , and although some epitopes mapped to similar locations in the two mA b, the maps for V-88 and F-423 were not identical. In MRL/Mp-lpr/lpr m ice, as lupus disease progressed there was a switch from IgM antibodie s to Ige anti-peptide antibodies whose specificity for the peptide ant igens coincided with but was better defined than that of the IgM antib odies. The identified idiotopes were located in both complementary det ermining regions (CDR) and framework region (FR) regions, indicating t hat some contribute to CRI shared by other related antibodies, while o thers were unique to either mAb V-88 or F-423. In conclusion, we have dissected and identified a mosaic of antibody V-region idiotopes that contribute to the idiotype of an anti-DNA autoantibody and against whi ch autoantibodies are made naturally in lupus disease.