Autoreactive CD4(+) T cells to beta(2)-glycoprotein I in patients with antiphospholipid syndrome.
Antiphospholipid syndrome (APS) is characterized by recurrent thrombosis and intrauterine fetal loss in association with antiphospholipid antibodies (aPL). We have recently identified autoreactive CD4(+) T cells to beta(2)-glycoprotein I (beta(2)GPI) that promote aPL production in APS patients. beta(2)GPI-specific CD4(+) T cells preferentially recognize the antigenic peptide containing the major phospholipid-binding site in the context of DRB4*0103 (DR53). T-cell receptor beta chains of beta(2)GPI-specific T cells are highly restricted and mainly utilize rearranged Vbeta7 or Vbeta8 gene segments. T-cell helper activity that stimulates B cells to produce anti-beta(2)GPI antibodies is mediated through IL-6 and CD40-CD40 ligand engagement. beta(2)GPI-specific T cells respond to reduced beta(2)GPI and recombinant beta(2)GPI fragments produced in bacteria, but not to native beta(2)GPI, indicating that the epitopes recognized by beta(2)GPI-specific T cells are apparently cryptic. Activation of beta(2)GPI-specific T cells resulting in production of pathogenic anti-beta(2)GPI antibodies can be induced by the exposure to cryptic peptides of beta(2)GPI. Finally, beta(2)GPI-specific T cell is a reasonable target of potential therapeutic strategies that selectively suppress pathogenic aPL production in APS patients.
Kuwana
Masataka
M
Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, 160-8582 Tokyo, Japan. kuwanam@sc.itc.keio.ac.jp
D000917:Antibody Formation / Q000276:immunology / Q000502:physiology; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology / Q000502:physiology; D015551:Autoimmunity / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D053482:beta 2-Glycoprotein I
D001323:Autoantibodies; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I