Analysis of autoantigens in aplastic anemia : identification of an epitope recognized by CD4^+ T cells specific to hematopoietic progenitor cells
| Project/Area Number |
15390298
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Kanazawa University |
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Principal Investigator |
NAKAO Shinji Kanazawa University, Graduate School of Medical Science, Professor, 大学院・医学系研究科, 教授 (70217660)
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| Co-Investigator(Kenkyū-buntansha) |
CHUHJO Tatsuya Kanazawa University Hospital, Instructor, 医学部附属病院, 助手 (00303298)
TAKAMI Akiyoshi Kanazawa University Hospital, Instructor, 医学部附属病院, 助手 (80324078)
OKAWA Katsuya KIRIN BREWERY Co.LTD, Pharmaceutical Division Discovery Research Group, Researcher, 医薬探索研究所, 研究員
ISHIYAMA Ken Kanazawa University Hospital, Instructor, 医学部附属病院, 助手 (60377380)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 2004: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥7,100,000 (Direct Cost: ¥7,100,000)
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| Keywords | aplastic anemia / autoantigen / moesin / DRS-1 / HLA-DR15 / PNH |
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| Research Abstract |
To identify an 80-kD protein derived from a leukemia cell line, UT-7, that was recognized by scrum IgG of a plastic anemia (AA) patients, we purified this protein using immunoprecipitation and determined amino acid sequence with mass fingerprinting. The protein proved to be moesin. When patients' sera were screened using ELISA and recombinant moesin, 20 of 43 (46.5%) AA patients were positive for anti-moesin antibodies. The antibody was detected in 14 of 22 (64%) patients possessing increased paroxysmal nocturnal hemoglobinuria (PNH)-type cells which are known to be a marker for lmmunopathophysiology of AA while it was detected in only 3 of 18 (17%) patients without increased PNH-type cells.
We also identified diazepam-binding inhibitor-related sequence-1 (DRS-1), as a candidate autoantigen of AA using immunoscreening of cDNA library derived from UT-7. Antibodies to this protein were detectable in 32 of 84 (38.1%) of AA patients possessing increased PNH-type cells. Epitope mapping using GST-fusion protein fragments derived from DRS-1 cDNA showed that a 26 mer peptide (amino acid 173-198) contained a hot spot of antibody epitopes which was recognized by nearly half of AA patients showing anti-DRS-1 antibodies. When peripheral blood lymphocytes were examined using ELISPOT assay for the presence of T-cell precursors specific to a DRS-1 peptide which has high affinity to HLA-DR15, two AA patients carrying HLA-DR15 and anti-DRS-1 antibodies showed high frequency of DRS-1-specific CD4^+ T cells. DRS-1-specific T cells generated from one of the two AA patients by stimulating T cells with the DRS-1 peptide showed cytotoxicity against an HLA-DR15^+ and DRS-1-expressing leukemia cell line KH88 in a dose-dependent manner. These findings indicate that in AA patients possessing HLA-DR15 and anti-DRS-1 antibodies, DRS-1-specific T cells may contribute to development of bone marrow failure.
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Report
(3 results)
Research Products
(20 results)
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[Journal Article] Expansion and activation of minor histocompatibility antigen HY-sipecific T cells associated with graft-versus-leukemia response.2004
Author(s)
Takami A, Sugimori C, Feng X, Yachie A, Kondo Y, Nishimura R, Kuzushima K, Kotani T, Asakura H, Shiobara S, Nakao S
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Journal Title
Bone Marrow Transplant 34-8
Pages: 703-709
Description
「研究成果報告書概要(欧文)」より
Related Report
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