CDNA SEQUENCE-ANALYSIS AND CHARACTERIZATION OF A CYTOKINE-INDUCING MONOCLONAL-ANTIBODY DERIVED FROM AUTOIMMUNE MRL MP-LPR/LPR MOUSE/

We have previously reported that a monoclonal antibody 1D11 derived fr om an autoimmune MRL/Mp-lpr/lpr (MRL/lpr) mouse induced synthesis or i ncreased production of IL-3, IL-6, and TNF-alpha in the IL-3-dependent bone marrow-derived cell line FDC-P2/185-4. In this report, we analyz ed a sequence of cDNA encoding the V region of 1D11, and found that V- H and V-L segments of 1D11 belonged to the J558 and V-kappa 21 family, respectively, The nucleotide sequence of 1D11 in the V-H Segment was highly homologous to that of AM9, a monoclonal RF derived from MRL/lpr mouse, and the only difference was the replacement of 3 nucleotides i n the framework region 1 (FR1), However, the deduced amino acid sequen ce of 1D11 was identical to that of AM9, In contrast with the V-H segm ent, the sequences of the V-L regions of these two antibodies were qui te different from each other; 1D11 showed a 3 base deletion in the FR2 and a 24 base insertion in the FR3 compared with AM9, At present, the mechanisms of such insertions or deletions in the FRs of autoantibodi es are almost unknown, It is generally accepted that the differences i n specificity and affinity of these autoantibodies depend on differenc es of CDR sequence, However, it is possible that not only CDRs but als o FRs of autoantibodies play a critical role in pathogenicity and/or s pecificity in autoimmune diseases.