ANALYSIS OF THE T CELL REPERTOIRE

当通过流式细胞术分析T细胞受体（TCR）表达时， 通过mRNA定量，检测到菌株特异性降低， 表达22种已知小鼠V β产物中的12种，代表 小鼠中潜在自身反应性T细胞的阴性选择 表达相应的自身配体。 这些缺失配体还 作为“超级抗原”，能够刺激T细胞表达 相应的Vbeta产品。 所有情况下的基因图谱 鉴定的内源性小鼠乳腺肿瘤（MMTV）前病毒编码 Vbeta特异性缺失配体。 这些Vbeta缺失没有发生在 无胸腺裸鼠，证明胸腺在耐受性中至关重要 负选择。 分析外源性病毒对T细胞的影响， 保留曲目。 牛奶传播的MMTV仅在以下菌株中诱导Vbeta-14缺失： 携带天然或转基因I-E II类主要组织相容性的小鼠 MHC复合体产物。 一种小鼠白血病病毒， 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。 尽管V β特异性超抗原效应是研究 TCR选择，选择可能更常见地取决于受体特异性 由多种TCR α和β链组分决定。 分析 特异性TCRVa/V β对的表达表明， Valpha/Vbeta配对是非随机的， 存在于Valpha/Vbeta表达模式中，提供了一种新的方法， 对剧目选择的研究。 T细胞对内源性 超抗原也显示出受Valpha和V β影响 TCR表达。 当在异种骨髓中分析TCR表达时， 小鼠和大鼠之间的移植，发现耐受性， 异种移植物伴随着V β特异性T细胞缺失。 在 小鼠CD 8 + T细胞对HIV肽的I类限制性反应，独特 交叉反应特异性模式伴随着高度 优先使用特定的Vbeta产品。

When T cell receptor (TCR) expression was analyzed by flow cytometry and by mRNA quantitation, strain-specific decreases were detected in expression of 12 of the 22 known mouse Vbeta products, representing negative selection of potentially self-reactive T cells in mice expressing the corresponding self ligands. These deleting ligands also functioned as "superantigens" capable of stimulating T cells expressing the corresponding Vbeta products. Genetic mapping in all cases identified endogenous mouse mammary tumor (MMTV) proviruses encoding the Vbeta-specific deleting ligands. These Vbeta deletions fail to occur in athymic nude mice, demonstrating that the thymus is critical in tolerance by negative selection. Exogenous viruses were analyzed for their influences on T cell repertoire. Milk-borne MMTV induced Vbeta-14 deletion only in strains of mice bearing natural or transgenic I-E class II major histocompatibility complex (MHC) product. A 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 Vbeta-5, followed later in the course of infection by widespread immune deficiency in all T cells. Although Vbeta-specific superantigen effects are a model for the study of TCR selection, selection may more commonly depend on receptor specificity determined by multiple TCR alpha and beta chain components. Analysis of the expression of specific TCR Valpha/Vbeta pairs has indicated that Valpha/Vbeta pairing is non-random and that strain-specific differences exist in patterns of Valpha/Vbeta expression, providing a new approach to the study of repertoire selection. T cell responses to endogenous superantigen were also shown to be influenced by Valpha as well as Vbeta TCR expression. When TCR expression was analyzed in xenogeneic bone marrow transplantation between mouse and rat, it was found that tolerance to xenograft was accompanied by Vbeta-specific T cell deletions. In the class I-restricted response of mouse CD8+ T cells to HIV peptides, unique cross-reactive specificity patterns were accompanied by highly preferential use of specific Vbeta products.