A peptide based on the CDR3 of an anti-DNA antibody of experimental SLE origin is also a dominant T-cell epitope in (NZBXNZW)F1 lupus-prone mice

A molecular homology has been demonstrated between sequences of the heavy c hain Variable regions of the anti-DNA, anti-cardiolipin monoclonal antibody , 2C4C2, isolated from C3H.SW mice with induced systemic lupus erythematosu s, and sequences of the anti-DNA monoclonal antibody BW16 originating in th e lupus-prone (NZBXNZW)F1 mice. It was of interest to determine whether the se homologous sequences function also as immunodominant T-cell epitopes, in order to establish a connection between spontaneous and induced experiment al models. Therefore, three peptides were designed and synthesized based on the complementarity determining region (CDR)1, CDR2 and CDR3 of the heavy chain of the monoclonal antibody 2C4C2. In the present study, we compare th ese peptides with the CDR1- and CDR3-based peptides of another murine anti- DNA antibody; namely, 5G12. The comparison was carried out by analyzing the ability of the peptides to induce T-cell activation in (NZBXNZW)F1 lupus-p rone mice and in mouse strains susceptible to induction of experimental sys temic lupus erythematosus. Immunization of(NZBXNZW)F1 mice with the 2C4C2 m Ab or with its CDR-based peptides, as well as immunization with the 5G12-ba sed CDR peptides, induced significant lymph node proliferation to the pCDR3 of the 5G12 mAb. Naive (NZBXNZW)F1 splenocytes exhibited activation to the same peptide. It is also shown that MHC class II molecules of (NZBXNZW)F1 macrophages bind preferentially the 5G12-based pCDR3. It is proposed that t he CDR3-based peptide of 5G12 mAb of experimental lupus is also a dominant and relevant epitope in the (NZBXNZW)F1 lupus-prone mice. (C) 2000 Elsevier Science B.V. All rights reserved.