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

Kazue Yoshida, Takahide Arai, Junichi Kaburaki, Yasuo Ikeda, Yutaka Kawakami, Masataka Kuwana

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2499-2504
Number of pages6
JournalBlood
Volume99
Issue number7
DOIs
Publication statusPublished - 2002 Apr 1

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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