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• W1989716637 endingPage "1896" @default.
• W1989716637 startingPage "1889" @default.
• W1989716637 abstract "Abstract Autoreactive CD4+ T cells to β2-glycoprotein I (β2GPI) that promote antiphospholipid antibody production were recently identified in patients with antiphospholipid syndrome (APS). To further examine antigen recognition profiles and T-cell helper activity in β2GPI-reactive T cells, 14 CD4+ T-cell clones specific to β2GPI were generated from 3 patients with APS by repeated stimulation of peripheral blood T cells with recombinant β2GPI. At least 4 distinct T-cell epitopes were identified, but the majority of the β2GPI-specific T-cell clones responded to a peptide encompassing amino acid residues 276 to 290 of β2GPI (KVSFFCKNKEKKCSY; single-letter amino acid codes) that contains the major phospholipid-binding site in the context of the DRB4*0103 allele. Ten of 12 β2GPI-specific T-cell clones were able to stimulate autologous peripheral blood B cells to promote anti-β2GPI antibody production in the presence of recombinant β2GPI. T-cell helper activity was exclusively found in T-cell clones capable of producing interleukin 6 (IL-6). In vitro anti-β2GPI antibody production induced by T-cell clones was inhibited by anti-IL-6 or anti-CD40 ligand monoclonal antibody. In addition, exogenous IL-6 augmented anti-β2GPI antibody production in cultures of the T-cell clone lacking IL-6 expression. These results indicate that β2GPI-specific CD4+ T cells in patients with APS preferentially recognize the antigenic peptide containing the major phospholipid-binding site and have the capacity to stimulate B cells to produce anti-β2GPI antibodies through IL-6 expression and CD40-CD40 ligand engagement. These findings are potentially useful for clarifying the pathogenesis of APS and for developing therapeutic strategies that suppress pathogenic antiphospholipid antibody production in these patients." @default.
• W1989716637 created "2016-06-24" @default.
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• W1989716637 date "2001-09-15" @default.
• W1989716637 modified "2023-09-30" @default.
• W1989716637 title "Autoreactive CD4+ T-cell clones to β2-glycoprotein I in patients with antiphospholipid syndrome: preferential recognition of the major phospholipid-binding site" @default.
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• W1989716637 doi "https://doi.org/10.1182/blood.v98.6.1889" @default.
• W1989716637 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11535526" @default.
• W1989716637 hasPublicationYear "2001" @default.
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