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

MHC 结合、SIV 衍生、CTL 和 HTL 表位

• 批准号: 8133326
• 负责人: David I Watkins
• 金额: $ 76.39万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2012-03-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8133326
• 关键词: AIDS vaccine development; Acquired Immunodeficiency Syndrome; Alleles; Amino Acids; Animal Model; Antigens; Binding; Biological Assay; Common Epitope; Communities; Cytotoxic T-Lymphocytes; Development; Enzymes; Epitopes; HIV; HIV vaccine; Helper-Inducer T-Lymphocyte; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Human; Immune response; In Situ; Individual; Infection; Knowledge; Length; Letters; Link; MHC Class I Genes; MHC Class II Genes; Macaca; Macaca mulatta; Measures; Methods; Modeling; Monitor; Open Reading Frames; Pathogenesis; Peptide/MHC Complex; Peptides; Play; Population; Reagent; Research Personnel; Role; SIV; Scanning; Sorting - Cell Movement; Spottings; Staining method; Stains; System; T-Lymphocyte; T-Lymphocyte Epitopes; Vaccinated; Vaccines; Viral; cohort; cytokine; pathogen; pre-clinical; public health relevance; response; synthetic peptide; tool

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.

描述（由申请人提供）：有3000多万艾滋病毒感染者，没有什么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）和辅助性T淋巴细胞（HTLs）在控制病毒复制中发挥的重要作用，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）、酶联斑点形成试验（ELISPOT）和四聚体染色。ICS和ELISPOT可以使用长度为10-15个氨基酸的肽进行检测。然而，取决于真正的表位在合成肽中的位置，这些肽集可能不能准确地检测免疫反应的大小。最小最优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隐式开放阅读框（corf）中存在几个MHC l类限制性表位。因此，我们建议在SIV的经典orf和隐orf中继续我们对印度恒河猴常见的I类和II类分子的最小最佳表位的定义。