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

估计感染艾滋病毒-1的4 000万人中有50%以上生活在撒哈拉以南非洲。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，因此迫切需要另一种方法来控制这种病毒的传播。一种很有希望的策略是生产一种疫苗，在疾病期间预防感染和/或增强对HIV-1的免疫力。免疫系统的细胞，即CD8+ T淋巴细胞，有效地控制HIV-1的生长，目前临床试验中的许多疫苗都旨在唤起CD8+ T细胞介导的免疫。然而，这种病毒与宿主免疫系统之间的相互作用是复杂的，病毒控制水平在HIV-1感染个体中是可变的。这反过来又使设计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类分子代表了影响疾病结果的重要宿主因子-这些分子指导CD8+ T细胞对HIV-1的反应，因此影响疾病的严重程度。通过研究不同HIV-1感染患者群体中不同CD8+ T细胞反应的细节，我希望找出为什么一些CD8+ T细胞反应比其他CD8+ T细胞反应在控制HIV-1复制方面更有效的原因。某些MHC I类分子也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HIV-1感染的疾病动力学。我还希望研究NK和MHC相互作用可能解释这一现象的方面，因为这可能影响未来疫苗方案的设计和实施。

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.