ANALYSIS OF THE T CELL REPERTOIRE

T 细胞库分析

• 批准号: 3774391
• 负责人: R J HODES
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3774391
• 关键词: MHC class II antigen; T cell receptor; T lymphocyte; cell population study; gene expression; genetically modified animals; immunogenetics; laboratory mouse; leukocyte activation /transformation; mouse mammary tumor virus; murine leukemia virus

Exogenous retroviruses were analyzed for their influences on T cell repertoire. A defective murine leukemia virus which causes a mouse acquired immune deficiency syndrome (MAIDS) induced superantigen-like T cell activation in vitro. In vivo, this virus selectively activated and expanded CD4+ T cells expressing V-beta5, followed later in the course of infection by widespread immune deficiency in all T cells. The effect of milk-borne MMTV on the T cell receptor (TCR) repertoire was analyzed. A previously uncharacterized tumorigenic milk-borne virus in BALB/c mice (the BALB/cV virus) was found to induce deletion of T cells expressing TCR V-beta2 in developing mice. This effect was MHC-dependent. The role of MHC class II molecules in susceptibility to MMTV infection was tested for the C3H MMTV. This milk-borne virus induced V-beta14 deletion only in strains of mice bearing natural or transgenic I-E class II major histocompatibility complex (MHC) product. Moreover, susceptibility to milk-borne virus as determined by as says of viral pp28 or LTR mRNA was also dependent upon I-E expression. These findings indicate that viral infection is dependent upon superantigenic stimulation of host lymphoid cells. Although V-beta-specific superantigenic effects are a useful model for the study of TCR selection, selection may more commonly be on the basis of receptor specificity determined by multiple TCR alpha and beta chain components. Analysis of the expression of specific TCR V-alpha/V-beta pairs has indicated that V-alpha/V-beta pairing is non-random and that strain-specific differences exist in patterns of V-alpha/V-beta expression, providing a new approach to the study of repertoire selection. T cell responses to endogenous superantigen were also shown to be influenced by V-alpha as well as V-beta TCR expression.

分析外源性逆转录病毒对T细胞的影响， 保留曲目。 一种有缺陷的小鼠白血病病毒， 获得性免疫缺陷综合征（MAIDS）诱导的超抗原样T 体外细胞活化。 在体内，这种病毒选择性地激活， 扩增的表达V-β 5的CD 4 + T细胞，随后在 所有T细胞中广泛免疫缺陷的感染。 研究了乳源性MMTV对T细胞受体（TCR）库的影响。 分析了 一种以前没有特征的致瘤性乳传播病毒， 发现BALB/c小鼠（BALB/cV病毒）诱导T细胞缺失 在发育中的小鼠中表达TCR V-β 2。 这种效应是MHC依赖性的。 MHC-II类分子在MMTV感染易感性中的作用， 测试了C3 H MMTV。 这种乳传播病毒诱导V-β 14缺失 仅在携带天然或转基因I-E II类主要 组织相容性复合体（MHC）产物。 此外， 如通过病毒pp 28或LTR mRNA所确定的， 也依赖于I-E表达。 这些发现表明， 感染依赖于宿主淋巴细胞的超抗原刺激 细胞 虽然V-β特异性超抗原效应是一个有用的模型， 在TCR选择的研究中，选择可能更常见地基于 由多个TCR α和β链决定的受体特异性 件. 特异性TCR V-α/V-β表达的分析 pairs已经表明V-α/V-β配对是非随机的， 在V-α/V-β模式中存在菌株特异性差异 表达，提供了一个新的方法来研究剧目的选择。 对内源性超抗原的T细胞应答也被证明是 受V-α以及V-β TCR表达的影响。