1993 Fiscal Year Annual Research Report

HTLV-1中和エピトープの同定および抗HTLV-1ペプチドワクチンの開発

Research Project

Project/Area Number	04670391
Research Institution	Kyushu University
Principal Investigator	中村稔九州大学, 医学部, 助手 (40217906)
Co-Investigator(Kenkyū-buntansha)	中野修治九州大学, 医学部助手, 助手 (40164248)
Keywords	Bリンパ球レパートリー / ヒト型モノクローナル抗体 / 抗HTLV-1 抗体 / 中和エピトープ / ペプチドワクチン / B Cell エピトープ / T Cell エピトープ / 抗ミトコンドリア抗体
Research Abstract	ヒト型の抗HTLV-1モノクローナル抗体(mAb)を用いて、HTLV-1の中和エピトープを詳細に解析した後、HTLV-1ペプチドワクチンの作製が可能か否かについて検討した。まず、HAM/TSP 患者未梢血Bリンパ球に Epstein Barr virus(EBV)を感染させ、HTLV-1envelope g1-ycoprotein(gp46)と結合する抗HTLV-1 mAbを多数作製した。153種のgp46と結合するmAbの内、24種が中和活性を有していた。これらの中和mAbの内、13種がgp46 peptide 175-199と反応し、1種がgp46 peptid 213-236に,他の1種がgp46 peptide 288-317と結合した。9種のmAbは結合するpeptidが同定できなかった。また、gp46peptid 175-199 と結合するmAbを用いて、4つの異なる中和エピトープ;(1)187-193,(2)191-196,(3)193-199,(4)continuous conformational B cell epitope,をその領域内に同定し、gp46a. a.187-199をprinciple neutralizing determinant(PND)と命名した。液相のペプチドを用いた競合実験により、PNDは natural gp46 proteinの中和エピトープと極めて類似した構造をとることから、ペプチドワクチンの良い候補と考えられた。そこで、PNDを含む様々なペプチドワクチンを合成し、ラットあるいはラビットに免疫し、高力価の中和抗体を誘導することに成功した。(J.Immunol inpress,1994) 今後、HTLV-1 T cell epitope の解析をさらにすすめ、より効率良く中和抗体を誘導するペプチドワクチンの開発を目指す予定である。

Research Products
(8 results)

All Other

All Publications (8 results)

[Publications] Eishi,Baba and Minoru,Nakamura et al.: "A peptide based HTLV-1 vaccine containing T and B cell epitopes which induces high titers of neutralizing antibodies." The Journal of Immunology. (in press). (1994)
[Publications] Minoru,Nakamura et al.: "Peripheral B lymphocyte repertoire to mitochondrial antigens in patients with primery biliary cirrhosis.-Positive correlation between the disease activity and the frecuency of ." Hepatology. (in press). (1994)
[Publications] Jun-ichi,Kira et al.: "Sequence heterogeneity of HTLV-1 proviral DNA in the central nervous system of patients with HTLV-1 associated myelopathy." Annuals of Neurology. (in press). (1994)
[Publications] Hideyuki,Ikematsu et al.: "VH and VK segment structure of anti-Insulim Ig G autoantibodies in patients with insulin-dependent diabetesmellitus.Evidence for somatic mutation.21GC04:The Journal of Immunology." (in press). (1994)
[Publications] Mieko,Matsui and Minoru,Nakamura et al.: "Human monocloxal autoantibodies apatient with primary biliary cirrhosiswhich recognize two distinct autoepitopes in the E2 component of the pyruvatedehydrogenase complex." Hepatology. 18. 1069-1077 (1993)
[Publications] Eishi,Baba and Minoru,Nakamura et al.: "Multiple neutralizing B cell epitopes of HTLV-1 identified by human monoclonal antibodies.-A basis for the design of an HTLV-1 peptide vaccine-." The Journal of Immunology.151. 1013-1024 (1993)
[Publications] Mika,Kuroki and Minoru,Nakamuraet al.: "Identification of new epitopes recognized by human monoclonal antibodies with neutralizing and antibody-dependent cellular cytotoxicity activities specific for HTLV-1." The Journal of Immunology.149. 940-948 (1992)
[Publications] Minoru,Nakamura and Paoro,Casali.: "Generation of human monoclonal autoantibedy-producing cell lines by Epstein-Barr virus(EVB)-transformation ofautoreactive B lymphocytes followed bysomatic cell hybridization." Immunomethods,Academic Press,Inc.San Diego U.S.A., 159-168 (1992)

1993 Fiscal Year Annual Research Report

HTLV-1中和エピトープの同定および抗HTLV-1ペプチドワクチンの開発

Principal Investigator

中村 稔 九州大学, 医学部, 助手 (40217906)

Research Products

[Publications] Eishi,Baba and Minoru,Nakamura et al.: "A peptide based HTLV-1 vaccine containing T and B cell epitopes which induces high titers of neutralizing antibodies." The Journal of Immunology. (in press). (1994)

[Publications] Minoru,Nakamura et al.: "Peripheral B lymphocyte repertoire to mitochondrial antigens in patients with primery biliary cirrhosis.-Positive correlation between the disease activity and the frecuency of ." Hepatology. (in press). (1994)

[Publications] Jun-ichi,Kira et al.: "Sequence heterogeneity of HTLV-1 proviral DNA in the central nervous system of patients with HTLV-1 associated myelopathy." Annuals of Neurology. (in press). (1994)

[Publications] Hideyuki,Ikematsu et al.: "VH and VK segment structure of anti-Insulim Ig G autoantibodies in patients with insulin-dependent diabetesmellitus.Evidence for somatic mutation.21GC04:The Journal of Immunology." (in press). (1994)

[Publications] Mieko,Matsui and Minoru,Nakamura et al.: "Human monocloxal autoantibodies apatient with primary biliary cirrhosiswhich recognize two distinct autoepitopes in the E2 component of the pyruvatedehydrogenase complex." Hepatology. 18. 1069-1077 (1993)

[Publications] Eishi,Baba and Minoru,Nakamura et al.: "Multiple neutralizing B cell epitopes of HTLV-1 identified by human monoclonal antibodies.-A basis for the design of an HTLV-1 peptide vaccine-." The Journal of Immunology.151. 1013-1024 (1993)

[Publications] Mika,Kuroki and Minoru,Nakamuraet al.: "Identification of new epitopes recognized by human monoclonal antibodies with neutralizing and antibody-dependent cellular cytotoxicity activities specific for HTLV-1." The Journal of Immunology.149. 940-948 (1992)

[Publications] Minoru,Nakamura and Paoro,Casali.: "Generation of human monoclonal autoantibedy-producing cell lines by Epstein-Barr virus(EVB)-transformation ofautoreactive B lymphocytes followed bysomatic cell hybridization." Immunomethods,Academic Press,Inc.San Diego U.S.A., 159-168 (1992)

中村稔九州大学, 医学部, 助手 (40217906)