ANALYSIS OF THE T CELL REPERTOIRE

T 细胞库分析

• 批准号: 6289243
• 负责人: RICHARD J. HODES
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 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/6289243
• 关键词: T cell receptor; T lymphocyte; acquired immunodeficiency; disease /disorder proneness /risk; gene expression; genetic strain; genetically modified animals; helper T lymphocyte; histocompatibility antigens; immunogenetics; laboratory mouse; leukocyte activation /transformation; milk; mouse mammary tumor virus; murine AIDSs; superantigens; virus infection mechanism

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 Vß5, 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 Vß2 in developing mice. The roles of MHC class II, TCR, and CD28 costimulatory molecules in susceptibility to MMTV infection were tested. Milk-borne virus induced Vß-specific 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 assays 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. Studies employing CD28-deficient mice indicated that CD28-dependent costimulus plays a role in Vß- specific T and B cell responses to in vivo challenge of adult mice with infectious MMTV. In contrast, Vß-specific deletion in response to neonatal challenge, as well as susceptibility to infectious milk-borne virus, appeared to be CD28-independent.The role of costimulation is being studied in T cell repertoire selection. Mice that are either over-expressing or deficient in costimulatory molecules B7-1 and B7-2 or the costimulatory receptor CD28 are being analyzed for expressed T cell repertoire. Endogenous proviral antigens as well as the effect of fetal-specific antigens in a T cell receptor transgenic model of pregnancy are being analyzed. - anitigen presentation, immune response, immunology, lymphocytes, receptors, T lymphocytes,

分析了外源性逆转录病毒对T细胞库的影响。有缺陷的鼠白血病病毒，导致小鼠获得的免疫缺陷综合征（女仆）在体外诱导超抗原样T细胞活化。在体内，该病毒在所有T细胞中都通过广泛的免疫缺乏症进行了选择性激活和扩展表达Vß5的CD4+ T细胞，然后分析了牛奶 - 荷型MMTV对T细胞受体（TCR）库的影响。在BALB/C小鼠（BALB/CV病毒）中，先前未表征的致瘤乳 - 传播病毒可诱导发育中的小鼠表达TCRVß2的T细胞缺失。测试了MHC II，TCR和CD28共刺激分子在对MMTV感染敏感性中的作用。牛奶 - 传播病毒仅在具有天然或转基因I-E II类主要组织相容性复合物（MHC）产物的小鼠菌株中诱导的Vß特异性缺失。此外，由病毒PP28或LTR mRNA测定的牛奶传播病毒的敏感性也取决于I-E表达。这些发现表明，病毒感染取决于宿主淋巴样细胞的超根刺激。采用CD28缺陷小鼠的研究表明，CD28依赖性costimulus在vβ特异性T和B细胞对具有感染性MMTV的成年小鼠体内挑战的反应中起作用。相比之下，Vß特定的缺失响应新生儿挑战，以及对传染性牛奶传播病毒的敏感性，似乎是无关CD28的。分析表达的T细胞库的小鼠B7-1和B7-2过度表达或不足的小鼠或B7-2或共刺激受体CD28。内源性前病毒抗原以及胎儿特异性抗原在T细胞受体转基因妊娠模型中的影响正在分析。 - 反反应，免疫反应，免疫学，淋巴细胞，受体，T淋巴细胞，