Dissection of HIV-1 CTL Escape Pathways

描述：清除体内HIV-1感染的细胞将是任何提供HIV-1感染功能或真正治愈方法的关键组成部分。最好定义的杀人豁免权 受感染细胞是CD 8+细胞毒性T淋巴细胞（CTL），其识别在受感染细胞表面上的人白细胞抗原I类分子上呈递的短病毒序列。然而，HIV-1显示出其序列的大量突变和可塑性，这在大多数情况下限制了CTL的功效。 该项目是一个详细的解剖的病毒学和免疫学因素的能力，艾滋病毒-1逃避CTL。它探讨了对病毒的约束和施加这些约束的免疫受体。与保护性与非保护性CTL应答相关的约束进行了比较，以及与自然感染与疫苗产生的抗HIV-1 CTL相关的约束。具体而言，我们建议： 目的：确定CTL对HIV-1的保护性和非保护性应答的表位逃逸空间，并比较自然感染和克隆疫苗诱导的TCR特性和HIV-1逃逸空间。

DESCRIPTION: Clearing HIV-1-infected cells in vivo will be a key component of any approach to provide functional or true cure of HIV-1 infection. The best-defined arm of immunity for killing infected cells is CD8+ cytotoxic T lymphocytes (CTLs), which recognize short viral sequences presented on Human Leukocyte Antigen Class I molecules on infected cell surfaces. However, HIV-1 displays massive mutation and plasticity of its sequences, which limits the efficacy of CTLs in most circumstances. This project is a detailed dissection of the virologic and immunologic factors underlying the ability of HIV-1 to evade CTLs. It explores the constraints imposed on the virus and the immune receptors imposing those constraints. The constraints associated with protective versus non-protective CTL responses are compared, as well as the constraints associated with natural infection versus vaccine-generated anti-HIV-1 CTLs. Specifically, we propose: To define CTL "epitope escape spaces" for protective and non-protective responses to HIV-1, and To compare TCR properties and HIV-1 escape spaces in natural infection to those elicited by a clonal vaccine.