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Blood, 1 April 2002, Vol. 99, No. 7, pp. 2499-2504
IMMUNOBIOLOGY
Restricted T-cell receptor  -chain usage by T cells
autoreactive to 2-glycoprotein I in patients with
antiphospholipid syndrome
Kazue Yoshida,
Takahide Arai,
Junichi Kaburaki,
Yasuo Ikeda,
Yutaka Kawakami, and
Masataka Kuwana
From the Institute for Advanced Medical Research and
the Department of Internal Medicine, Keio University School of
Medicine, Tokyo; and the Department of Internal Medicine, Tokyo
Electric Power Company Hospital, Japan.
We recently identified CD4+ T cells that are
autoreactive to  2-glycoprotein I (2GPI)
and that promote antiphospholipid antibody production in patients with
antiphospholipid syndrome (APS). In this study, T-cell receptor (TCR)
chains of 2GPI-reactive T cells were examined in 8 2GPI-responders, including 5 patients with APS 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
2GPI. The TCR V segments that expanded oligoclonally after stimulation with 2GPI varied among responders, but
the V7 and V8 segments were commonly detected in 6 and 4 2GPI-responders, respectively. Analysis of the
complementarity-determining region 3 sequence of
2GPI-reactive T cells revealed limited diversity, and
all V7+ TCRs had an amino acid motif of TGxxN/Q or minor
variations. The V8+ TCRs had another motif, PxAxxD/E.
Surprisingly, an identical V7+ TCR chain was used by
2GPI-reactive T cells in 3 patients with APS. There was
no apparent difference in the TCR usage between APS patients and
healthy responders. Some of the V7+ TCRs with the
TGxxN/Q motif detected by PCR-SSCP analysis were also used by
2GPI-specific CD4+ T-cell clones responsive
to an immunodominant epitope containing the major phospholipid-binding
site. Depletion of V7+ or V8+ T cells
from the peripheral blood mononuclear cell cultures significantly inhibited in vitro anti-2GPI antibody production in
response to 2GPI. Our results indicate preferential
usage of TCR chains by 2GPI-reactive T cells. These
TCR chains can be reasonable targets for TCR-based immunotherapy for
patients with APS.
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