Restricted T-cell receptor P-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 B-2-glycoprotein I (beta(2)GPI) and that promote antiphospholipid antibody production in patients with antiphospholipid syndrome (APS). In this study, T-cell receptor (TCR) beta chains of beta(2)GPI-reactive T cells were examined in 8 B(2)GPI-responders,including 5 patients with AIRS and 3 healthy subjects, using polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) analysis combined with in vitro stimulation of peripheral blood T cells with recombinant beta(2)GPI. The TCR V-beta segments that expanded oligoclonally after stimulation with beta(2)GPI varied among responders, but the Vbeta7 and Vbeta8 segments were commonly detected in 6 and 4 beta(2)GPI-responders, respectively. Analysis: of the complementarity-determining region 3 sequence of beta(2)GPI-reactive T cells revealed limited diversity, and all Vbeta7(+) TCRs had an amino acid motif of TGxxN/Q or minor variations. The Vbeta8(+) TCRs had another motif, PxAxxD/E. Surprisingly, an identical VP7(+) TCRP chain was used by beta(2)GPI-reactive T cells in 3 patients with APS. There was no apparent difference in the TCRP usage between APS patients and,healthy responders. Some of the Vbeta7(+) TCRs with the TGxxN/Q motif detected by 1 PCR-SSCP analysis were also used by beta(2)GPI-specific CD4+ T-cell clones responsive to an immunodominant epitope containing the major phospholipid-binding site. Depletion of Vbeta7(+) or Vbeta8(+) T cells from the peripheral blood mononuclear cell cultures significantly inhibited in vitro anti-beta(2)GPI antibody production in response to beta(2)GPI. Our results indicate preferential usage of TCRbeta chains by beta(2)GPI-reactive T cells. These TCRbeta chains can be reasonable targets for TCR-based immunotherapy for patients with APS. (C) 2002 by The American Society of Hematology.