2000 Fiscal Year Annual Research Report

胸腺におけるT細胞レパトワ決定機構の解明

Research Project

Project/Area Number	11694289
Research Institution	Kyushu University
Principal Investigator	笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)
Co-Investigator(Kenkyū-buntansha)	山本健九州大学, 生体防御医学研究所, 助手 (60274528) 白澤専二九州大学, 生体防御医学研究所, 助手 (10253535) 福井宣規九州大学, 生体防御医学研究所, 助教授 (60243961)
Keywords	胸腺内T細胞分化 / 正の選択 / 抗原ペプチド / MHC / TCR / T細胞レパートリー
Research Abstract	T細胞は胸腺での分化過程において、そのTCRによるMHC/自己抗原ペプチド複合体の認識の結果、正及び負の選択を受け、免疫応答に寄与するT細胞レパートリーが形成される。我々は2つのアプローチを用いてT細胞レパートリー形成の分子機構の解明を試みた。第1に、1アミノ酸残基のみ異なる2種類の自己抗原ペプチド上で分化したT細胞レパートリーを比較することにより、自己抗原ペプチドのアミノ酸残基の側鎖の大きさや荷電の有無がT細胞レパートリーの多様性に影響を与えることを明らかにした。第2に、TCRα鎖のミニジーンを導入したトランスジェニックマウスの様々な分化段階の胸腺細胞上で発現するTCRを詳細に解析することにより、正の選択を経てある特定のTCRα鎖の頻度が増加することを見出した。以上の結果より、正の選択において自己抗原ペプチドが重要であり、特異的TCR-ペプチド相互作用を通じてT細胞レパートリーの偏りが生じる可能性が示唆された。また、研究分担者であるD.Mathis教授の研究室よりC.Benoist教授が2月末に九州大学・生体防御医学研究所を訪れ、セミナーを行うと同時に、今後の共同研究についての討議を行った。

Research Products
(11 results)

All Other

All Publications (11 results)

[Publications] Wataya M et al.: "Comparative analysis of HLA restriction and cytokine production of hepatitis B surface antigen-specific T cells from low-and high-antibody responders in vaccinated humans."J.Human Genet.. in press. (2001)
[Publications] Correia-Neves M et al.: "The shaping of the T cell repertoire."Immunity. 14. 21-32 (2001)
[Publications] Baba I et al.: "Involvement of deregulated epiregulin expression in tumorigenesis in vivo through activated Ki-Ras signaling pathway in human colon cancer cells."Cancer Res.. 60. 6886-6889 (2000)
[Publications] Ries S et al.: "Opposing effects of Ras on p53 : transcriptional activation of mdm2 and induction of p19^<ARF>."Cell. 103. 321-330 (2000)
[Publications] Shirasawa S et al.: "Rnx deficiency results in congenital central hypoventilation."Nature Genet.. 24. 287-289 (2000)
[Publications] Dilworth FJ et al.: "ATP-driven chromation ATP-driven chromatin remodeling activities and coactivator histone acetyltransferases act sequentially during transcriptional activation by RAR/RXR heterodimers in vitro."Molecular Cell. 6. 1049-1058 (2000)
[Publications] Fukui Y et al.: "Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor-contact."Proc.Natl.Acad.Sci.USA. 97. 13760-13765 (2000)
[Publications] Kawamura K et al.: "Induction of autoimmune encephalitis by proteolipid protein 95-116-specific T cells from HLA-DR2 (DRB1*1502) transgenic mice."J.Clin.Invest.. 105. 977-984 (2000)
[Publications] Toh H et al.: "Magnitude of structural changes of the T-cell receptor binding regions determine the strength of T-cell antagonism : molecular dynamics simulations of HLA-DR4(DRB1*0405)complxed with analogue peptide."Protein Engineering. 13. 423-429 (2000)
[Publications] Hamaguchi K et al.: "Analysis of tumor necrosis factor-a promoter polymphopism in type 1 diabetes : HLA-B and -DRB1 alleles are primarily associated with the disease in Japanese."Tissue Antigens. 55. 10-16 (2000)
[Publications] Witherden N et al.: "Tetracycline-controllable selection of CD4+T cells : half-life and survival signals in the absence of MHC class II molecules."J.Exp.Med.. 191. 355-364 (2000)

2000 Fiscal Year Annual Research Report

胸腺におけるT細胞レパトワ決定機構の解明

Principal Investigator

笹月 健彦 九州大学, 生体防御医学研究所, 教授 (50014121)

Research Products

[Publications] Wataya M et al.: "Comparative analysis of HLA restriction and cytokine production of hepatitis B surface antigen-specific T cells from low-and high-antibody responders in vaccinated humans."J.Human Genet.. in press. (2001)

[Publications] Correia-Neves M et al.: "The shaping of the T cell repertoire."Immunity. 14. 21-32 (2001)

[Publications] Baba I et al.: "Involvement of deregulated epiregulin expression in tumorigenesis in vivo through activated Ki-Ras signaling pathway in human colon cancer cells."Cancer Res.. 60. 6886-6889 (2000)

[Publications] Ries S et al.: "Opposing effects of Ras on p53 : transcriptional activation of mdm2 and induction of p19^<ARF>."Cell. 103. 321-330 (2000)

[Publications] Shirasawa S et al.: "Rnx deficiency results in congenital central hypoventilation."Nature Genet.. 24. 287-289 (2000)

[Publications] Dilworth FJ et al.: "ATP-driven chromation ATP-driven chromatin remodeling activities and coactivator histone acetyltransferases act sequentially during transcriptional activation by RAR/RXR heterodimers in vitro."Molecular Cell. 6. 1049-1058 (2000)

[Publications] Fukui Y et al.: "Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor-contact."Proc.Natl.Acad.Sci.USA. 97. 13760-13765 (2000)

[Publications] Kawamura K et al.: "Induction of autoimmune encephalitis by proteolipid protein 95-116-specific T cells from HLA-DR2 (DRB1*1502) transgenic mice."J.Clin.Invest.. 105. 977-984 (2000)

[Publications] Toh H et al.: "Magnitude of structural changes of the T-cell receptor binding regions determine the strength of T-cell antagonism : molecular dynamics simulations of HLA-DR4(DRB1*0405)complxed with analogue peptide."Protein Engineering. 13. 423-429 (2000)

[Publications] Hamaguchi K et al.: "Analysis of tumor necrosis factor-a promoter polymphopism in type 1 diabetes : HLA-B and -DRB1 alleles are primarily associated with the disease in Japanese."Tissue Antigens. 55. 10-16 (2000)

[Publications] Witherden N et al.: "Tetracycline-controllable selection of CD4+T cells : half-life and survival signals in the absence of MHC class II molecules."J.Exp.Med.. 191. 355-364 (2000)

笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)