ANALYSIS OF EPSTEIN BARR/VIRUS C3D RECEPTORS IN T LYMPHOCYTES

EB病毒（EBV）是传染性腮腺炎的病原体， 单核细胞增多症并与某些人类肿瘤有关。 EBV 靶向其宿主细胞结合到特定的表面糖蛋白， 145 kD大小。 这种受体也与第三种成分相互作用 补体C3，因此它被称为补体 2型受体，简称CR2。 越来越多的证据表明EBV与T淋巴细胞癌有关， 特别是与其他病毒感染如HIV相关。 的 我们实验室最近的工作特别令人感兴趣， EBV与T淋巴瘤的关系 我们已经证明受体 对于EBV，其在T谱系细胞上表达，特别是在未成熟的 胸腺细胞 此外，胸腺细胞可在暴露于免疫球蛋白后被感染。 病毒和病毒，沿着白细胞介素2，可以导致 以协同方式促进胸腺细胞增殖。 为了研究胸腺细胞CR2的生物学特性，我们 通过用HTLV-1感染产生胸腺细胞克隆。 一分离的 被称为TC 91+的克隆表达相对高量的CR2， 需要白细胞介素2才能生长 TC 91+细胞将被 通过免疫荧光进行表型的充分表征， 利用针对各种淋巴细胞单克隆抗体的免疫沉淀 分化和活化标志物。 TC 91+中编码CR2的基因 细胞将被克隆、测序并与已知基因进行比较。 的 EBV感染TC 91+细胞的能力和HTLV-1对此的影响 将研究感染。 最后，CR2的生物学效应 通过将TC 91+暴露于CR2配体如C3， EBV、EBV-gp 350和抗CR2单克隆抗体。 正在提供上述拟议工作的主要资金来源 美国国立卫生研究院赠款GM 39518，从1992年12月1日至1995年11月30日提供支持， 计划届时进行竞争性更新。 EB病毒的重要性 以及拟议工作与生物医学的相关性 预计将吸引和激励合格的少数民族学生， 参与研究。 参与研究的学生提出， 以上人员将在校长的直接监督下工作 调查员，并将在技术和学术上进行互动， 与实验室其他成员的水平。 以前的记录 在成功培训少数民族学生的调查，他的 科研项目积极活跃，经费保障水平良好 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.