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.
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 alphabeta 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.
Brosh
N
N
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Eilat
E
E
Zinger
H
H
Mozes
E
E
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D000911:Antibodies, Monoclonal / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D004247:DNA / Q000276:immunology; D005260:Female; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D010455:Peptides / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D018418:Th2 Cells / Q000276:immunology* / Q000637:transplantation
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007135:Immunoglobulin Variable Region; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA