MHC-bound, SIV-derived, CTL and HTL Epitopes

描述(由申请人提供)：在3000多万艾滋病毒感染者中，几乎没有比生产有效的艾滋病毒疫苗更紧迫的生物医学优先事项了。鉴于细胞毒性T淋巴细胞(CTL)和辅助T淋巴细胞(HTL)在控制病毒复制中的重要作用，这种疫苗刺激这些细胞反应是至关重要的。目前检测疫苗诱导的免疫反应的方法包括细胞内细胞因子染色(ICS)、酶联斑点形成分析(ELISPOT)和四聚体染色。ICS和ELISPOT可以使用长度为10-15个氨基酸的多肽进行。然而，根据真实表位在合成肽中的位置，这些肽集可能无法准确检测免疫反应的大小。最小最佳表位的确定是准确评估细胞免疫反应的最佳方法。此外，四聚体的合成完全依赖于最小最佳表位的知识。最后，我们最近发现在SIV隐蔽开放阅读框架(CORF)中存在几个MHC类L限制性表位。因此，我们建议在SIV中继续我们对普通印度恒河猴第一类和第二类分子最小最佳表位的定义，包括经典ORF和神秘ORF。 公共卫生相关性(由申请人提供)：印度恒河猴的SIV感染是研究HIV感染人类的最佳动物模型。印度恒河猴免疫后的SIV挑战是可用于HIV疫苗临床前开发的最佳定义模型之一。在这个具有重要生物医学意义的系统中，MHC等位基因的鉴定和SIV特异性表位的定义对免疫反应的定义至关重要。

DESCRIPTION (provided by applicant): With more than 30 million HIV-infected individuals, there can be few other more pressing biomedical priorities than to produce an effective vaccine for HIV. Given the important role that cytotoxic T lymphocytes (CTLs) and helper T lymphocytes (HTLs) play in controlling viral replication, it is critical that this vaccine stimulates these cellular responses. Current methods of detecting vaccine-induced immune responses include Intra-Cellular Cytokine Staining (ICS), Enzyme-Linked Spot-Forming Assays (ELISPOT), and tetramer staining. ICS and ELISPOT can be carried out using peptides of 10-15 amino acids in length. However, depending on where the true epitope lies in the synthetic peptide, these peptide sets may not accurately detect the magnitude of the immune response. The identification of minimal optimal epitopes is the best method to accurately assess cellular immune responses. Furthermore, the synthesis of tetramers is absolutely dependent on knowledge of the minimal optimal epitope. Finally, we recently discovered that there are several MHC class l-restricted epitopes in SIV cryptic Open Reading Frames (cORFs). We, therefore, propose to continue our definition of minimal optimal epitopes for common Indian rhesus macaque class I and II molecules in both classical and cryptic ORFs in SIV. PUBLIC HEALTH RELEVANCE (provided by applicant): SIV infection in Indian rhesus macaques is the best animal model for studying HIV-infected humans. SIV challenge of vaccinated Indian rhesus macaques is one of the best defined models available for pre-clinical development of HIV vaccines. Identification of MHC alleles and definition of SIV-specific epitopes is critical in the definition of the immune response in this biomedically important system.