ANALYSIS OF EPSTEIN BARR/VIRUS C3D RECEPTORS IN T LYMPHOCYTES

EB病毒(Epstein-Barr Virus，EBV)是传染性支气管炎的病原体。 单核细胞增多症，与某些人类肿瘤有关。EB病毒 通过与其特定的表面糖蛋白结合来靶向宿主细胞 大小为145kD。该受体还与第三组分相互作用。 补体的级联，C3，因此被称为补体 受体2型，简称CR2。 越来越多的证据表明EB病毒与T淋巴细胞癌有关， 特别是与艾滋病毒等其他病毒感染相关的。这个 我们实验室最近的工作特别令人感兴趣 EB病毒与T淋巴瘤的相关性。我们已经证明了受体 因为EBV表达在T系的细胞上，尤其是幼稚细胞 胸腺细胞。此外，胸腺细胞在接触到 病毒和病毒，以及白介素2，可以导致 胸腺细胞以协同方式增殖。 为了研究胸腺细胞上CR2的生物学特性，我们已经 通过感染HTLV-1产生胸腺细胞克隆。其中一个孤立的人 被称为TC91+的克隆表达相对较高数量的CR2和它 它的生长需要白介素2。TC91+细胞将是 通过免疫荧光和免疫荧光对表型进行了彻底的表征 利用抗多种淋巴细胞的单抗进行免疫沉淀 分化和激活标记。TC91+中CR2基因的编码 细胞将被克隆、测序并与已知基因进行比较。这个 EB病毒感染TC91+细胞的能力及HTLV-1对其影响 将对感染进行研究。最后，CR2的生物学效应 微扰将通过将TC91+暴露于诸如C3的Cr2配体来测试， EBV、EBV-gp350和抗CR2单抗。 上述拟议工作的主要资金来源正在提供。 由NIH拨款GM39518提供从1992年12月1日到1995年11月30日的支持， 计划在那时进行竞争性续签。EBV的重要性 在人类疾病和拟议的工作与生物医学的相关性 预计将吸引和激励合格的少数族裔学生成为 参与了这项研究。参与研究的学生提出了 以上工作将在校长的直接监督下进行 研究人员，并将在技术和学术上进行互动 与实验室其他成员的水平。之前的记录 成功培养少数民族学生的调查员，他的 积极主动的研究计划和良好的资金保障水平 有利于学习和研究培训的环境。

The Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis and is associated with certain human neoplasias. EBV targets its host cells by binding to a specific surface glycoprotein of 145 kD in size. This receptor also interacts with the third component of the complement cascade, C3 and thus it has been termed complement receptor type 2, abbreviated CR2. Increasing evidence implicated EBV in cancers of T lymphocytes, particularly in association with other viral infections such as HIV. The recent work from our laboratory is of particular interest to the association of EBV with T lymphomas. We have demonstrated that receptors for EBV are expressed on cells of the T lineage, particularly immature thymocytes. Furthermore, thymocytes can be infected upon exposure to the virus and the virus, along with Interleukin 2, can cause the proliferation of thymocytes in a synergistic fashion. In order to study the biological properties of CR2 on thymocytes, we have generated thymocyte clones by infection with HTLV-1. One of the isolated clones, termed TC91+, expresses relatively high amounts of CR2 ad it requires Interleukin 2 for its growth. The TC91+ cells will be thoroughly characterized phenotypically by immunofluorescence and immunoprecipitation utilizing monoclonal antibodies to various lymphocyte differentiation and activation markers. The gene coding for CR2 in TC91+ cells will be clones, sequenced and compared to the known gene. The ability of EBV to infect TC91+ cells and the effects of HTLV-1 upon this infection will be studied. Finally, the biologic effects of CR2 perturbation will be tested by exposing TC91+ to CR2 ligand such as C3, EBV, EBV-gp350, and anti-CR2 monoclonal antibodies. The main source of funding for the work proposed above is being furnished by NIH grant GM39518 which provides support from 12/1/92 to 11/30/95 with plans to be competitively renewed at that time. The importance of EBV in human disease and the relevance of the proposed work to biomedicine is expected to attract and motivate qualified minority students to be involved in the research. The students involved in the studies proposed above will be working under the direct supervision of the principal investigator and will be interacting at both the technical and academic levels with other members of the laboratory. The previous track record of the investigator in successfully training minority students, his vigorous and active research program, and good level of funding guarantee an environment conducive to learning and research training.