Restricted T-cell receptor β-chain usage by T cells autoreactive to β₂-glycoprotein I in patients with antiphospholipid syndrome

We recently identified CD4⁺ T cells that are autoreactive to β₂-glycoprotein I (β₂GPI) and that promote antiphospholipid antibody production in patients with antiphospholipid syndrome (APS). In this study, T-cell receptor (TCR) β chains of β₂GPI-reactive T cells were examined in 8 β₂GPI-responders, including 5 patients with APS and 3 healthy subjects, using polymerase chain reaction and single-strand conformation polymorphism (PCRSSCP) analysis combined with in vitro stimulation of peripheral blood T cells with recombinant β₂GPI. The TCR Vβ segments that expanded oligoclonally after stimulation with β₂GPI varied among responders, but the Vβ7 and Vβ8 segments were commonly detected in 6 and 4 β2GPI-responders, respectively. Analysis of the complementarity-determining region 3 sequence of β₂GPI-reactive T cells revealed limited diversity, and all Vβ7⁺ TCRs had an amino acid motif of TGxxN/Q or minor variations. The Vβ8⁺ TCRs had another motif, PxAxxD/E. Surprisingly, an identical Vβ7⁺ TCRβ chain was used by β₂GPI-reactive T cells in 3 patients with APS. There was no apparent difference in the TCRβ usage between APS patients and healthy responders. Some of the Vβ7⁺ TCRs with the TGxxN/Q motif detected by PCR-SSCP analysis were also used by β₂GPI-specific CD4⁺ T-cell clones responsive to an immunodominant epitope containing the major phospholipid-binding site. Depletion of Vβ7+ or Vβ8⁺ T cells from the peripheral blood mononuclear cell cultures significantly inhibited in vitro anti-β₂GPI antibody production in response to β2GPI. Our results indicate preferential usage of TCRβ chains by β₂GPI-reactive T cells. These TCRβ chains can be reasonable targets for TCR-based immunotherapy for patients with APS.