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Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 July 2001, Vol. 98, No. 1, pp. 130-139 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY 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, and Yasuo Ikeda From the Institute for Advanced Medical Research and the Department of Internal Medicine, Keio University School of Medicine, Tokyo; the Department of Internal Medicine, Tokyo Electric Power Company Hospital; the Department of Microbiology, Kitasato University School of Medicine, Sagamihara; and the Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan. 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 GPIIb or GPIIIa were generated and tested for their ability to stimulate antigen-specific T-cell proliferation and anti-GPIIb-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 GPIIb and GPIIIa (IIb18-259 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 IIb18-259 and IIIa22-262 were consistently detected, whereas those to other fragments were sometimes lost. In vitro antigenic stimulation of peripheral blood mononuclear cells with IIb18-259 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 IIb18-259, IIIa22-262, or both. T-cell lines reactive to IIb18-259 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 GPIIb and GPIIIa. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Yu, S. Heck, V. Patel, J. Levan, Y. Yu, J. B. Bussel, and K. Yazdanbakhsh Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura Blood, August 15, 2008; 112(4): 1325 - 1328. [Abstract] [Full Text] [PDF] H. Sukati, H. G. Watson, S. J. Urbaniak, and R. N. Barker Mapping helper T-cell epitopes on platelet membrane glycoprotein IIIa in chronic autoimmune thrombocytopenic purpura Blood, May 15, 2007; 109(10): 4528 - 4538. [Abstract] [Full Text] [PDF] M. Sakakura, H. Wada, Y. Abe, J. Nishioka, H. Tomatsu, Y. Hamaguchi, S. Oguni, H. Shiku, and T. 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[Full Text] [PDF] M. Kuwana, Y. Kawakami, and Y. Ikeda Suppression of autoreactive T-cell response to glycoprotein IIb/IIIa by blockade of CD40/CD154 interaction: implications for treatment of immune thrombocytopenic purpura Blood, January 15, 2003; 101(2): 621 - 623. [Abstract] [Full Text] [PDF] M. Kuwana, Y. Okazaki, J. Kaburaki, Y. Kawakami, and Y. Ikeda Spleen Is a Primary Site for Activation of Platelet-Reactive T and B Cells in Patients with Immune Thrombocytopenic Purpura J. Immunol., April 1, 2002; 168(7): 3675 - 3682. [Abstract] [Full Text] [PDF] D. B. Cines and V. S. Blanchette Immune Thrombocytopenic Purpura N. Engl. J. Med., March 28, 2002; 346(13): 995 - 1008. [Full Text] [PDF]

	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020