Siliciano R F, Lawton T, Knall C, Karr R W, Berman P, Gregory T, Reinherz E L
Laboratory of Immunobiology Dana-Farber Cancer Institute Harvard Medical School Boston, Massachusetts 02115.
Cell. 1988 Aug 12;54(4):561-75. doi: 10.1016/0092-8674(88)90078-5.
The primary human T cell response to HIV was analyzed by isolating from seronegative donors T cell clones specific for HIV gp120. T cell epitopes restricted by different MHC elements were identified within gp120, and synthetic peptides were used to address the fundamental problem of how HIV sequence variability affects T cell recognition. Even one conservative substitution can drastically reduce recognition; thus the interaction of gp120 epitopes with T cell receptors and MHC is precise and poorly crossreactive. Importantly, a subset of CD4+ gp120-specific clones manifest cytolytic activity and lyse uninfected autologous CD4+Ia+ T cells in the presence of gp120 in a process that is strictly dependent upon CD4-mediated uptake of gp120 by T cells. Assuming gp120 is shed from HIV-infected cells in vivo, this novel CD4-dependent autocytolytic mechanism may contribute to the profound depletion of CD4+ cells in AIDS.
通过从血清阴性供体中分离出针对HIV gp120的T细胞克隆，分析了人类T细胞对HIV的主要反应。在gp120中鉴定出受不同MHC元件限制的T细胞表位，并使用合成肽来解决HIV序列变异性如何影响T细胞识别这一基本问题。即使是一个保守性替换也能显著降低识别能力；因此，gp120表位与T细胞受体和MHC的相互作用是精确的，且交叉反应性很差。重要的是，一部分CD4+ gp120特异性克隆表现出细胞溶解活性，并在gp120存在的情况下裂解未感染的自体CD4+Ia+ T细胞，这一过程严格依赖于T细胞对gp120的CD4介导摄取。假设gp120在体内从HIV感染细胞中脱落，这种新的CD4依赖性自细胞溶解机制可能导致艾滋病中CD4+细胞的严重耗竭。
