CD7 AND LYMPHOCYTE DEVELOPMENT AND FUNCTION

弗朗西斯科·A·博尼拉拥有医学博士和免疫学博士学位。 在接受了儿科临床培训后，获得了 在波士顿儿童医院的过敏/免疫学，他最近 被任命为免疫学教研室教授 机构。博尼拉博士现在计划继续担任科学家内科医生 进行基础免疫学研究，最终目标是 成为一名独立的调查员。博尼拉博士的工作将是 在以下分部的研究设施内进行 儿童医院免疫学。 大量文献有力地表明，淋巴细胞 表面标志CD7在肿瘤的发生和发展中起着重要作用 多个白细胞系的功能。然而，CD7的配体 而且它的信号通路仍然未知。我们将使用以下方法 有针对性的基因破坏，创造出缺乏CD7的小鼠。这将提供 一个明确定义CD7在人类社会中的重要性的系统 表达CD7缺陷的细胞的发育和功能 将对小鼠进行淋巴细胞代表的研究 流动在初级和次级淋巴组织中的亚群 细胞计数和免疫组织化学方法。他们将在未来面临挑战 用几种抗原和它们的抗体反应评估活体。他们 还将接受一系列全面的体外测试 T细胞、B细胞和自然杀伤细胞的功能。 我们还将研究CD7细胞内部分的相互作用 有信号通路。我们将创建一些混合结构 由人CD8分子的外部部分连接而成的 人CD7的胞质结构域。CD7域名将受到 不同的突变和缺失；转染了这些基因的细胞 我们将从几个生物学效应的角度来研究构造 与CD7结扎相关。 此外，我们将使用酵母双杂交系统来鉴定 与CD7的胞内结构域相关的蛋白质。互动 蛋白质将被克隆和测序。我们将尝试确定 通过结构比较，它们在信号传递中的潜在作用 已知蛋白质，以及通过分析磷酸化模式 在细胞刺激之后。

Francisco A. Bonilla holds both M.D. and Ph.D. (Immunology) degrees. Following clinical training in Pediatrics, and a fellowship in Allergy/Immunology at Children's Hospital, Boston, he has recently been appointed to the faculty of the Division of Immunology at this institution. Dr. Bonilla now plans to continue as a Scientist Physician performing basic Immunology research, with the eventual goal of becoming an independent investigator. Dr. Bonilla's work will be carried out within the research facilities of the Division of Immunology of Children's Hospital. A large body of literature strongly suggests that the lymphocyte surface marker CD7 has an important role in the development and function of a number of leukocyte lineages. However, the ligand for CD7 and its signaling pathways remain unknown. We will use the method of targeted gene disruption to create mice lacking CD7. This will provide a system in which to clearly define the importance of CD7 in the development and function of the cells which express it CD7-deficient mice will be studied with respect to the representation of lymphocyte subpopulations in primary and secondary lymphoid tissues by flow cytometry, and immunohistochemical methods. They will be challenged in vivo with several antigens and their antibody responses assessed. They will also be subjected to a comprehensive battery of in vitro tests of T cell, B cell, and natural killer cell function. We will also study the interaction of the intracellular portion of CD7 with signaling pathways. We will create a number of hybrid constructs consisting of the external portion of the human CD8 molecule joined to the cytoplasmic domain of human CD7. The CD7 domain will be subjected to various mutations and deletions; cells transfected with these constructs will be studied with respect to several biological effects associated with CD7 ligation. In addition, we will employ the yeast two hybrid system to identify proteins associated with the intracellular domain of CD7. Interacting proteins will be cloned and sequenced. We will attempt to determine their potential roles in signaling through structural comparisons with known proteins, as well as by analyzing phosphorylation patterns following cellular stimulation.