Identification of T cell epitopes and development of a new immunotherapy for idiopathic thrombocytopenic purpura
| Project/Area Number |
16590942
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Ehime University |
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Principal Investigator |
HATO Takaaki Ehime University, University Hospital, Lecturer, 医学部附属病院, 講師 (30172943)
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| Co-Investigator(Kenkyū-buntansha) |
YASUKAWA Masaki Ehime University, School of Medicine, Professor, 医学部, 教授 (60127917)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | platelet / ITP / GPIIb-IIIa / T cell / autoimmunity / integrin / epitope |
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| Research Abstract |
The purpose of this study is to define the role and dominant epitopes of GPIIb-reactive T cells in idiopathic thrombocytopenic purpura (ITP). We established a CD4^+ T cell line recognizing the GPIIb #429-443 amino acid sequence in a HLA-DR^*0405-restricted manner from an ITP patient. Interferon-gamma production was detected when the cells were co-cultured autologous immature dendritic cells which had been loaded with platelet lysate, suggesting that the region around GPIIb 429-443 can be presented to CD4^+ T cells in the context of HLA-DRB1^*0405. We isolated further T cell clones from several ITP patients. These clones were mainly CD4^+ helper T cells, but CD8^+ cytotoxic T cells could also be isolated. To measure helper activity of T cells, we established a sandwich ELISA assay for GPIIb antibody using anti-GPIIb-IIIa monoclonal antibodies produced in our laboratory. Then we reported WT1-specific and HLA class II-restricted CD4^+ T cells possessing direct cytotoxic activity against leukemia cells, indicating establishment of specific assay for cytotoxic activity of CD4^+ T cells. We also reported that perforin is expressed constitutively in memory CD8^+ cytotoxic T cells, but is dependent on cell activation in memory CD4^+ cytotoxic T cells, suggesting differential regulation of cytotoxicity in CD4^+ and CD8^+ T cells. Then we attempted to identify the amino acid regions critical for GPIIb-IIIa activation using alanine-scaninng mutagenesis. We identified three amino acids critical for ligand binding to GPIIb-IIIa and an amino acid motif in the intracellular domain of GPIIb that suppresses GPIIb-IIIa activation.
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Report
(3 results)
Research Products
(23 results)
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[Journal Article] Direct recognition and lysis of leukemia cells by WT1-specific CD4^+ T lymphocytes in an HLA class II-restricted manner.2005
Author(s)
Guo Y, Niiya H, Azuma T, Uchida N, Yakushijin Y, Saki I, Hato T, Takahashi M, Senju S, Nishimura Y, Yasukawa M
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Journal Title
Blood 106(4)
Pages: 1415-1418
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Existence of leukemic clones resistant to both imatinib mesylate and rituximab before drug therapies in a patient with Philadelphia chromosome-positive acute lymphocytic leukemia.2004
Author(s)
Hato T, Yamanouchi J, Tamura T, Hojo N, Niiya Y, Kohno M, Bando S, Yakushijin Y, Takada K, Sakai I, Yasukawa M, Fujita S.
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Journal Title
International Journal of Haematology 80(1)
Pages: 62-66
NAID
Description
「研究成果報告書概要(欧文)」より
Related Report
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