Characterization and role in experimental systemic lupus erythematosus of T‐cell lines specific to peptides based on complementarity‐determining region‐1 and complementarity‐determining region‐3 of a pathogenic anti‐DNA monoclonal antibody

Summary Peptides based on the complementarity‐determining region 1 (CDR1) and CDR3 of an anti‐DNA monoclonal antibody (mAb) carrying the 16/6 idiotype (Id) were shown to induce experimental systemic lupus erythematosus (SLE) in susceptible mouse strains. In the present study, T‐cell lines specific to the pCDR1 and pCDR3 peptides were established in BALB/c and in SJL mice, respectively. The T‐cell lines were characterized and analysed for their pathogenicity upon administration to syngeneic mouse strains. Both T‐cell lines expressed the αβ T‐cell receptor (TCR) and the CD4 +  CD8 – phenotype. Additionally, both cell lines secreted interleukin (IL)‐4 and IL‐10 upon stimulation with their specific peptide, thus belonged to the T helper 2 (Th2) subset. Upon immunization, the pCDR3‐specific T‐cell line induced experimental SLE in SJL mice. The animals produced high levels of autoimmune anti‐DNA and antinuclear protein antibodies, as well as anti‐16/6 Id antibodies (Abs). Furthermore, the mice developed clinical manifestations, including leukopenia, proteinuria and accumulation of immune complex deposits in their kidneys. The pCDR1‐specific T‐cell line failed to induce SLE when injected into BALB/c mice. It is thus suggested that pCDR3 is an immunodominant epitope in experimental SLE and that pCDR3‐specific T cells initiate autoimmunity, leading to SLE, probably via epitope spreading.