Monoclonal anti-double-stranded DNA antibodies cross-react with phosphoglycerate kinase 1 and inhibit the expression and production of IL-2 in activated Jurkat T cell line.
Anti-double strand DNA antibodies (anti-dsDNA) involve in lupus nephritis. However, their role in tissue damage mechanism remains unclear. In this study, a 45-kDa cognate antigen of anti-dsDNA monoclonal antibodies 9D7 was identified by two-dimensional gel electrophoresis and determined to be human phosphoglycerate kinase 1 (PGK-1) by MALDI-TOF analysis. The binding of 9D7 to PGK-1 was not affected by DNase I but was inhibited by thymus dsDNA. Human SLE sera with high anti-dsDNA titers had a high affinity with PGK. In activated Jurkat T cells, 9D7 decreased the PGK-1 mRNA production and IL-2 promoter activity. Reduction in IL-2 gene expression and protein production were observed in the 9D7-treated cells. Because PGK-1 deficiency may cause mental tardy and hemolytic anemia, interaction between anti-dsDNA and PGK-1 may be important in lupus pathogenesis. Moreover, reduction in IL-2 production by anti-dsDNA suggests their role in increasing infection rate and decreasing proper generation of activation-induced cell death.
Luan
Hui-Ying
HY
Faculty of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Department of Education and Research, Taipei City Hospital, Taiwan.
Tang
Shye-Jye
SJ
Yang
Winnie
W
Tsai
Chang-Youh
CY
Sun
Guang-Huan
GH
Sun
Kuang-Hui
KH
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D003429:Cross Reactions; D016207:Cytokines / Q000235:genetics; D004247:DNA / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D019169:Jurkat Cells; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D010735:Phosphoglycerate Kinase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D014158:Transcription, Genetic
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D016207:Cytokines; D007376:Interleukin-2; D012333:RNA, Messenger; D004247:DNA; D010735:Phosphoglycerate Kinase; D000469:Alkaline Phosphatase