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A study on T cell differentiation, selection and T cell receptors

T细胞分化、选择和T细胞受体的研究

基本信息

批准号：
03454192
负责人：
ONOE Kazunori
金额：
$ 3.97万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454192/
关键词：
Thymus T cell differentiation Positive selection Negative selection CD4^-8^-Programd cell death NK1^+TCRalphabeta cell Fas antigen positive selection negative selection programmed cell death NK1.1^+TCRαβ^+胸腺細胞 CD4^+8^-T細胞骨髄キメラ

项目摘要

1. Expression of Mtv-7, the genetic locus of an endogenous mammary tumor virus which determines the minor lymphocyte stimulatory (Mls--1^<a\0> phenotype, results in the deletion of the cells that express Vbeta 6, 7, 8.1, or 9 among developing thymocytes. By using allogeneic [Mls-1^b -> Mls-1^a] bone marrow chimeras, we have demonstrated that within the recipient thymus Mls-1^a reactive T cells are eliminated from the developing thymocyte population that is derived from the donor bone marrow. In the present study we have investigated the tolerogenicity of Mls-1^a antigen derived from host T cells which represent a major population of radio-resistant cells in the [Mls-1^b -> Mls-1^a] chimeras. We found that recipient T cells which can survive lethal irradiation and produce intrinsic superantigens alter eventually the T cell repertoire in the thymus which have been developing from precursors of donor bone marrow.2. An NK1.1^+TCRalphabeta^<low> thymocyte subpopulation was identified. This subpopulation exhibited cytotoxicity against CD4^+8^+ immature thymocytes from syngeneic and allogeneic mice. The cytotoxicity was shown to be mediated by Fas-Fas ligand interaction.3. A monoclonal antibody (2H2) which is specific for a src-family tyrosine kinase, Fgr, has been established. We could idntify Fgr positive macrophages in lymph nodes and spleen. The Fgr was shown to be associated with Ly6C and seveeral proteins.4. A gretopic motifs on pigeon cytochrome c related peptides were determined. On the basis of these agretopic motifs, we could produce synthetic peptide vaccines against influenza viras.

1. mv -7是一种内源性乳腺肿瘤病毒的遗传位点，它决定了小淋巴细胞刺激（Mls- 1^<a\0>表型）的表达，导致发育中的胸腺细胞中表达vβ 6、7、8.1或9的细胞缺失。通过使用同种异体[Mls-1^b -> Mls-1^a]骨髓嵌合体，我们已经证明在受体胸腺中，Mls-1^a反应性T细胞从来自供体骨髓的发育中的胸腺细胞群中被消除。在本研究中，我们研究了来自宿主T细胞的Mls-1^a抗原的耐受性，这些T细胞代表了[Mls-1^b -> Mls-1^a]嵌合体中主要的放射抗性细胞群。我们发现受体T细胞能够在致死照射下存活并产生固有的超抗原，最终改变了胸腺中由供体骨髓前体发育而来的T细胞库。鉴定出NK1.1^+ tcrα β ^<低>胸腺细胞亚群。该亚群对同基因和异基因小鼠的CD4^+8^+未成熟胸腺细胞表现出细胞毒性。细胞毒性是由Fas-Fas配体相互作用介导的。已经建立了一种针对src家族酪氨酸激酶Fgr的单克隆抗体（2H2）。我们可以在淋巴结和脾脏中发现Fgr阳性巨噬细胞。Fgr被证明与Ly6C和几种蛋白质有关。测定了鸽子细胞色素c相关肽的一个异位基序。在这些异位基序的基础上，我们可以合成抗流感病毒的肽疫苗。