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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. Mtv-7是决定次要淋巴细胞刺激（Mls-1）表型的内源性乳腺肿瘤病毒的遗传基因座，Mtv-7的表达导致发育中的胸腺细胞中表达V β 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内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消除。在本研究中，我们研究了来源于宿主T细胞的Mls-1 ^a抗原的耐受性，所述宿主T细胞代表[Mls-1 ^b-> Mls-1 ^a]嵌合体中的主要放射抗性细胞群体。我们发现，受者T细胞能够在致死辐射中存活并产生内在超抗原，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NK 1.1 ^+ TCR α ^<low>胸腺细胞亚群。该亚群对来自同基因和异基因小鼠的CD 4 ^+8^+未成熟胸腺细胞表现出细胞毒性。细胞毒作用是由Fas与Fas配体相互作用介导的.建立了一种针对src家族酪氨酸激酶Fgr的单克隆抗体（2 H2）。在淋巴结和脾脏中可见到Fgr阳性的巨噬细胞。Fgr被证明与Ly 6C和细胞蛋白相关。测定了鸽细胞色素c相关肽的一个Gretopic基序。基于这些互补序列，我们可以合成抗流感病毒的多肽疫苗。