RESEARCH OF THE STRUCTURE AND BINDING BETWEEN T CELL RECEPTOR AND ANTIGEN-PRESENTING MOLECULE IN THE ALLERGIC DISEASE

变态反应性疾病中T细胞受体与抗原呈递分子的结构及结合研究

• 批准号: 12670742
• 负责人: INOUE Ryosuke
• 金额: $ 2.18万
• 依托单位: GIFU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670742/
• 关键词: BETA-LACTOGLOBULIN; ANTIGEN-SPECIFIC T CELL; HLA; TCR; CDR3; IL-4; IFN-GAMMA RATIO; ANALOGUE-PEPTIDE THERAPY; T細胞クローン; HLA class II; T細胞受容体

(1) Six TCCs established from the five patients responded to three different peptide fragments, and the fragment of BLGp97-117 was recognized most frequently by the T cells. BLGp101-112 (KYLLFCMENSAE) was the core sequence to be recognized in this portion.(2) Milk allergy group was higher than control group in possession ratio of HLA-DRB1^*0405 allele, but there was not significant difference between both groups. HLA-DRB1^*0405 allele participate in BLG-recognition profoundly.(3) Sequence analysis of TCR with RT-PCR method revealed a striking heterogeneity and similar patterns of amino acid sequence were recognized in the CDR3 region.(4) Analysis of cytokine production revealed high levels of IL-5 production by antigen-specific T cell lines of all ; IL-4 and IFN-γ were also produced in a variety of degree by these T cell lines. The differences in the ratios of IL-4 to IFN-γ might explain the differences in their clinical features.(5) We substituted another amino acid for an amino acid of BLGp101-111 by one and composed several analogue peptides. The T cell clone reacted to only the peptides with similar property. Biochemical property of the antigen can prescribe the T cell response in the allergic patho-genesis. We aim development of the novel therapy using analogue peptides that induce Th1-typed T-cell response.

(1)5名患者建立的6个TCC对三种不同的肽片段有反应，其中BLGp97-117片段被T细胞识别最频繁，是该部分识别的核心序列。 (2)牛奶过敏组HLA-DRB1^*0405等位基因的拥有率高于对照组，但两组间差异无统计学意义。 HLA-DRB1^*0405等位基因深刻参与BLG识别。(3)RT-PCR方法对TCR的序列分析显示出显着的异质性，在CDR3区域识别出相似的氨基酸序列模式。(4)细胞因子分析生产表明，所有抗原特异性 T 细胞系均产生高水平的 IL-5；这些 T 细胞系也不同程度地产生 IL-4 和 IFN-γ。IL-4 的比例存在差异。 (5)我们将BLGp101-111中的一个氨基酸替换为另一种氨基酸，组成了几种类似肽，T细胞克隆仅对具有相似性质的肽发生反应。抗原的生化特性可以决定过敏发病机制中的 T 细胞反应，我们的目标是使用诱导 Th1 型 T 细胞反应的类似肽来开发新疗法。

项目成果

Matsui E., Kaneko H., Teramoto T., Fukao T., Inoue R., Kasahara K., Takemura M., Seishima M., Kondo N.: "Reduced IFN-gamma production in response to IL-12 stimulation and/or reduced IL-12 production in atopic patients"Clin. Exp. Allergy. 30. 1250-1256 (20

Matsui E.、Kaneko H.、Teramoto T.、Fukao T.、Inoue R.、Kasahara K.、Takemura M.、Seishima M.、Kondo N.：“IL-12 刺激和反应导致 IFN-γ 产生减少

Kondo N., Matui E., Kaneko H., Kato Z., Fukao T., Teramoto T.,Inoue R., Watanabe M., Sakaguchi H., Kasahara K., Morinoto N.: "Role of IL-12 receptor β 2 mutations in the development of atopy"ACI International supplement. No. 1. 92-94 (2000)

Kondo N.、Matui E.、Kaneko H.、Kato Z.、Fukao T.、Teramoto T.、Inoue R.、Watanabe M.、Sakaguchi H.、Kasahara K.、Morinoto N.：“IL-12 的作用受体β2突变在特应性发展中的作用”ACI国际增刊.No.1.92-94(2000)

Kondo N., Matui E., Kaneko H., Kato Z., Fukao T., Teramoto T., Inoue R., Watanabe M., Sakaguchi H., Kasahara K., Morimoto N.: "Reduced interferon-γ production and mutations of the IL-12 receptor β 2 chain gene in atopic subjects"Int. Arch. Allergy. Immuno

Kondo N.、Matui E.、Kaneko H.、Kato Z.、Fukao T.、Teramoto T.、Inoue R.、Watanabe M.、Sakaguchi H.、Kasahara K.、Morimoto N.：“减少干扰素-γ 的产生和特应性受试者中 IL-12 受体 β 2 链基因的突变“Int. Arch. Allergy.Immuno

Kondo N., Matsui E., Kaneko H., Fukao T., Teramoto T.,Inoue R., Watanabe M., Aoki M., Kasahara K., Morimoto N.: "Atopy and mutations of IL-12 receptor β 2 chain gene"Clin. Exp. Allergy. 31. 1189-93 (2001)

Kondo N.、Matsui E.、Kaneko H.、Fukao T.、Teramoto T.、Inoue R.、Watanabe M.、Aoki M.、Kasahara K.、Morimoto N.：“IL-12 受体 β 的特应性和突变2链基因”Clin. Exp. Allergy. 31. 1189-93 (2001)

Kondo N, et al.: "Reduced interferon-γ production and mutations of the interleukin-12 receptor β2 chain gene in atopie subjects"Int Arch Allergy Immunol.. 124. 117-120 (2001)

Kondo N 等人：“特应性受试者中干扰素 γ 的产生减少以及白细胞介素 12 受体 β2 链基因的突变” Int Arch Allergy Immunol.. 124. 117-120 (2001)