Immunodominant epitopes on glycoprotein IIb-IIIa recognized by autoreactive T cells in patients with immune thrombocytopenic purpura

Masataka Kuwana, Junichi Kaburaki, Hidero Kitasato, Miyako Kato, Shinichi Kawai, Yutaka Kawakami, Yasuo Ikeda

Research output: Contribution to journalArticle

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Abstract

It was recently reported that autoreactive CD4+ T cells to glycoprotein IIb-IIIa (GPIIb-IIIa) mediate antiplatelet autoantibody production in patients with immune thrombocytopenic purpura (ITP). To further examine the antigenic specificity of the GPIIb-IIIa-reactive T cells, 6 recombinant fragments encoding different portions of GPIIbα or GPIIIa were generated and tested for their ability to stimulate antigen-specific T-cell proliferation and antiGPIIb-IIIa antibody production in vitro. T cells from the peripheral blood of 25 patients with ITP and 10 healthy donors proliferated in response to recombinant GPIIb-IIIa fragments in various combinations. The amino-terminal portions of both GPIIbα and GPIIIa (IIbα18-259 and IIIa22-262) were frequently recognized (60% and 64%, respectively) compared with other fragments (4%-28%) in patients with ITP, but this tendency was not detected in healthy donors. In subsequent analyses in patients with ITP, T-cell reactivities to IIbα18-259 and IIIa22-262 were consistently detected, whereas those to other fragments were sometimes lost. In vitro antigenic stimulation of peripheral blood mononuclear cells with IIbα18-259 or IIIa22-262 promoted the synthesis of anti-GPIIb-IIIa antibodies in patients with ITP, but not in healthy donors. Of 15 CD4+ T-cell lines specific for platelet-derived GPIIb-IIIa generated from 5 patients with ITP, 13 lines recognized IIbα18-259, IIIa22-262, or both. T-cell lines reactive to IIbα18-259 or IIIa22-262 promoted the production of anti-GPIIb-IIIa antibodies that were capable of binding to normal platelet surfaces. These results indicate that the immunodominant epitopes recognized by pathogenic CD4+ T cells in patients with ITP are located within the amino-terminal portions of both GPIIbα and GPIIIa.

Original languageEnglish
Pages (from-to)130-139
Number of pages10
JournalBlood
Volume98
Issue number1
DOIs
Publication statusPublished - 2001 Jul 1

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Immunodominant Epitopes
Platelet Glycoprotein GPIIb-IIIa Complex
Idiopathic Thrombocytopenic Purpura
T-cells
T-Lymphocytes
Integrin beta3
Tissue Donors
Platelets
Antibodies
Blood
Blood Platelets
Cell Line
Cell proliferation
Autoantibodies
Antibody Formation
Epitopes
Blood Cells
Cell Proliferation
Antigens

ASJC Scopus subject areas

  • Hematology

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Immunodominant epitopes on glycoprotein IIb-IIIa recognized by autoreactive T cells in patients with immune thrombocytopenic purpura. / Kuwana, Masataka; Kaburaki, Junichi; Kitasato, Hidero; Kato, Miyako; Kawai, Shinichi; Kawakami, Yutaka; Ikeda, Yasuo.

In: Blood, Vol. 98, No. 1, 01.07.2001, p. 130-139.

Research output: Contribution to journalArticle

Kuwana, M, Kaburaki, J, Kitasato, H, Kato, M, Kawai, S, Kawakami, Y & Ikeda, Y 2001, 'Immunodominant epitopes on glycoprotein IIb-IIIa recognized by autoreactive T cells in patients with immune thrombocytopenic purpura', Blood, vol. 98, no. 1, pp. 130-139. https://doi.org/10.1182/blood.V98.1.130
Kuwana, Masataka ; Kaburaki, Junichi ; Kitasato, Hidero ; Kato, Miyako ; Kawai, Shinichi ; Kawakami, Yutaka ; Ikeda, Yasuo. / Immunodominant epitopes on glycoprotein IIb-IIIa recognized by autoreactive T cells in patients with immune thrombocytopenic purpura. In: Blood. 2001 ; Vol. 98, No. 1. pp. 130-139.
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