Aspects of CD8+ T cell and NK cell recognition that impact on MHC class I associations with HIV-1 disease progression

CD8 T 细胞和 NK 细胞识别影响 MHC I 类与 HIV-1 疾病进展的关联

• 批准号: G0501011/1
• 负责人: Geraldine Gillespie
• 金额: $ 41.17万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0501011%2F1
• 关键词: Aspects; CD8+; cell; NK; recognition

Over 50% of the 40 Million people estimated to be infected with HIV-1 live in sub-Saharan Africa alone. With only a small proportion of developing countries having access to the anti-retroviral therapies readily available in the Western world, an alternative approach is urgently required to control the spread of this virus. One promising strategy is the production of a vaccine to either prevent infection and/or augment immunity against HIV-1 during disease. Cells of the immune system, namely CD8+ T lymphocytes, effectively control the growth of HIV-1, and many vaccines in current clinical trials are designed to evoke CD8+ T cell mediated immunity.The interaction between this virus and the host s immune system is complex, however, and the level of viral control is variable in HIV-1 infected individuals. This, in turn, makes it difficult to design a truly effective HIV vaccine. Major Histocompatibility Complex (MHC) class I molecules represent important host factors that influence disease outcome - these molecules direct the CD8+ T cell responses against HIV-1, and therefore influence disease severity. By studying the fine details of diverse CD8+ T cell responses in distinct HIV-1 infected patient groups I hope to identify the reasons why some CD8+ T cell responses are more effective than others in controlling the replication of HIV-1. Certain MHC class I molecules also interact with different cells of the immune system, namely Natural Killer (NK) cells, and this also impacts on disease dynamics in HIV-1 infection. I also wish to study aspects of NK and MHC interactions that might explain this phenomenon, as this could influence the design and implementation of future vaccine regimens.

在估计感染HIV-1的4000万人中，仅撒哈拉以南非洲就有超过50%的人生活在那里。由于只有一小部分发展中国家能够获得西方世界现成的抗逆转录病毒疗法，迫切需要另一种方法来控制这种病毒的传播。一个有希望的策略是生产一种疫苗，以预防感染和/或在疾病期间增强对艾滋病毒-1的免疫力。免疫系统中的细胞，即CD8+T淋巴细胞能够有效地控制HIV-1的生长，目前临床试验中的许多疫苗都是为了激发CD8+T细胞介导的免疫。然而，这种病毒与宿主S免疫系统之间的相互作用是复杂的，而且对HIV-1感染者的病毒控制水平是不同的。这反过来又使得设计一种真正有效的艾滋病毒疫苗变得困难。主要组织相容性复合体(MHC)I类分子是影响疾病结局的重要宿主因素--这些分子指导CD8+T细胞对HIV-1的反应，从而影响疾病的严重程度。通过研究不同HIV-1感染人群中不同CD8+T细胞反应的细节，我希望找出为什么某些CD8+T细胞反应在控制HIV-1复制方面比其他更有效的原因。某些MHC I类分子还与免疫系统的不同细胞，即自然杀伤(NK)细胞相互作用，这也影响了HIV-1感染的疾病动态。我还希望研究NK和MHC相互作用的一些方面，以解释这种现象，因为这可能会影响未来疫苗方案的设计和实施。