Dissection of HIV-1 CTL Escape Pathways

描述：清除体内的HIV-1感染细胞将是任何提供功能性或真正治疗HIV-1感染的方法的关键组成部分。最清晰的杀戮豁免权 感染细胞是CD8+细胞毒性T淋巴细胞(CTL)，识别感染细胞表面人类白细胞抗原I类分子上的短病毒序列。然而，HIV-1的ITS序列表现出大量的突变和可塑性，这限制了CTL在大多数情况下的疗效。 这个项目是对HIV-1逃避CTL能力的病毒学和免疫学因素的详细剖析。它探讨了对病毒施加的限制以及施加这些限制的免疫受体。与保护性和非保护性CTL反应相关的约束，以及与自然感染和疫苗产生的抗HIV-1 CTL相关的约束进行了比较。具体来说，我们建议： 确定针对HIV-1的保护性和非保护性反应的CTL“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.