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

描述（由申请人提供）：有超过3000万艾滋病毒感染者，可能有一些其他更紧迫的生物医学优先事项比生产一种有效的艾滋病毒疫苗。鉴于细胞毒性T淋巴细胞（CTL）和辅助性T淋巴细胞（HTLs）在控制病毒复制中发挥的重要作用，该疫苗刺激这些细胞反应至关重要。目前检测疫苗诱导的免疫应答的方法包括细胞内细胞因子染色（ICS）、酶联斑点形成测定（ELISPOT）和四聚体染色。ICS和ELISPOT可以使用长度为10-15个氨基酸的肽进行。然而，取决于真实表位位于合成肽中的位置，这些肽组可能无法准确检测免疫应答的大小。最小最佳表位的鉴定是准确评估细胞免疫应答的最佳方法。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）中存在多个MHC I类限制性表位。因此，我们建议继续我们的定义最小的最佳表位共同印度恒河猴类I和II分子在经典和神秘的ORF SIV。 公共卫生相关性（由申请人提供）：印度恒河猴中的SIV感染是研究HIV感染者的最佳动物模型。接种疫苗的印度恒河猴的SIV攻击是HIV疫苗临床前开发的最佳定义模型之一。MHC等位基因的鉴定和SIV特异性表位的定义对于定义这个生物医学重要系统中的免疫反应至关重要。

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.