MECHANISMS OF PATHOGENESIS AND RECOVERY IN FRIEND RETROVIRUS-INDUCED LEUKEMIA

该项目包括旨在阐明基因控制的 宿主防御机制参与自发恢复， 对Friend鼠逆转录病毒诱导的白血病的保护性免疫。 MHC基因在自发性恢复和免疫应答中起重要作用。 接种疫苗引起的保护性免疫。 我们最近的结果显示 I-Ab基因或Db基因的点突变 足以抑制自发恢复。 I-Ab基因作为 典型的免疫反应基因，促进T辅助细胞对 Friend病毒包膜蛋白。 Db基因似乎会影响 病毒特异性细胞毒性T淋巴细胞的发育。 这些细胞 与体内的实际恢复过程密切相关， 目前的数据表明，它们对病毒包膜具有特异性， 蛋白 Db单倍型可以通过以下方式促进恢复： 选择某些病毒包膜肽作为免疫裂解的靶。 在该系统中，通过接种 灭活的全病毒或纯化的病毒包膜蛋白， 表达病毒包膜蛋白的重组牛痘病毒。 的 I-Ab基因在介导成功应答中起重要作用， 免疫，但缺乏这种基因的动物可以得到保护， 免疫接种是用一种强有力的佐剂进行的。 近期的数据表明 一些可用于人类的合成疫苗也能 在该模型中增强成功的免疫保护。

This project contains studies aimed at elucidating genetically controlled host defense mechanisms involved in spontaneous recovery and protective immunity against Friend murine retrovirus-induced leukemia. MHC genes play an important role both in spontaneous recovery and in protective immunity induced by vaccination. Our recent results show that point mutations in either the I-Ab gene or the Db gene are sufficient to inhibit spontaneous recovery. The I-Ab gene acts as a typical immune response gene facilitating the T helper cell response to Friend virus envelope protein. The Db gene appears to influence development of virus-specific cytotoxic T lymphocytes. These cells are strongly associated with the actual recovery process in vivo, and our current data indicates that they are specific for the viral envelope protein. The Db haplotype may operate to facilitate recovery by selecting certain viral envelope peptides as targets for immune lysis. Protective immunity can be induced in this system by inoculation with killed whole virus or purified viral envelope protein in adjuvant or recombinant vaccinia virus expressing the viral envelope protein. The I-Ab gene is important in mediating a successful response to immunization, but animals lacking this gene can be protected if immunization is done using a powerful adjuvant. Recent data indicates that some synthetic vaccines feasible for use in humans also work to potentiate successful immune protection in this model.