Autoreactive CD4+ T cells to β2-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 β2-glycoprotein I (β2GPI) that promote aPL production in APS patients. β2GPI-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 β chains of β2GPI-specific T cells are highly restricted and mainly utilize rearranged Vβ7 or Vβ8 gene segments. T-cell helper activity that stimulates B cells to produce anti-β2GPI antibodies is mediated through IL-6 and CD40–CD40 ligand engagement. β2GPI-specific T cells respond to reduced β2GPI and recombinant β2GPI fragments produced in bacteria, but not to native β2GPI, indicating that the epitopes recognized by β2GPI-specific T cells are apparently cryptic. Activation of β2GPI-specific T cells resulting in production of pathogenic anti-β2GPI antibodies can be induced by the exposure to cryptic peptides of β2GPI. Finally, β2GPI-specific T cell is a reasonable target of potential therapeutic strategies that selectively suppress pathogenic aPL production in APS patients.