ANALYSIS OF CYTOTOXIC T CELL RESPONSES IN SIV INFECTED SOOTY MANGABEYS

SIV 感染的乌白眉猴细胞毒性 T 细胞反应分析

• 批准号: 6591320
• 负责人: A KAUR
• 金额: $ 11.11万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6591320
• 关键词: AIDS; Mammalia; communicable diseases; immunology; inflammation; lymphatic system; virus

Sooty mangabeys are African Old World primates that are naturally infected with SIV, have high plasma SIV levels and yet do not progress to AIDS To understand the immune basis of this protected state, SIV-specific CTL activity was studied in sooty mangabeys with natural SIV infection and following experimental infection with SIVmac239 SIV-specific CTL activity was analysed in 12 naturally infected sooty mangabeys SIV-specific CTL were not detectable in fresh PBMC from 7 of 7 animals, even when tested at high effector to target ratios, suggesting the absence of circulating activated SIV-specific CTL Following ex vivo antigen-specific stimulation, the response was heterogeneous Vigorous SIV-specific CTL activity was detectable in only 4/12 animals It remained undetectable or inconsistently present in 5/12 animals and detectable at low levels in 3/12 animals No correlation was observed between the magnitude of viral load and the strength of SIV-specific CTL activity SIV-specific CTL clones were isolated from SIVmac239 and naturally infected sooty mangabeys Clones with activity against gag, env and nef proteins mapped to highly conserved regions of the SIV genome An env-specific epitope maps to a highly conserved 9-mer peptide, YVPCHIRQI, located just beyond the V4 region of gp120, while a gag epitope was localized to a 12-mer peptide in p27 (aa 281-292) These epitopes are immunodominant, as bulk CTL lysed targets presenting the epitope to an extent comparable to targets expressing the entire protein A single nef-specific CTL clone was isolated from a naturally infected sooty mangabey and the 20-mer epitope maps to aa 21-40 Follow up of these animals may shed light on the interactions between virus and CTL that result in apathogenic SIV infection

乌龟是非洲东半球的灵长类动物，自然是 感染了SIV，血浆SIV水平较高，但没有进展 以了解这种受保护状态的免疫基础， 研究了SIV特异性CTL活性在煤烟芒果鱼中的作用。 SIV感染和SIVmac239实验性感染 分析了12例自然感染的煤烟中SIV特异性CTL活性 在新鲜的PBMC中未检测到MANGABYS SIV特异性CTL 7只动物，即使在高效应器与靶标比率下进行测试， 提示缺乏循环激活的SIV特异性CTL 在体外抗原特异性刺激后，反应是 检测到异质性的SIV特异性CTL活性 只有4/12的动物保持检测不到或不一致的存在 在5/12的动物中，在3/12的动物中可检测到低水平 观察到病毒载量的大小和 SIV特异性CTL活性克隆的强度为 从SIVmac239分离到自然感染的煤质芒果克隆 抗Gag、env和nef蛋白的活性被高度定位 SIV基因组的保守区域环境特异性表位映射到 高度保守的9-肽YVPCHIRQI，位于V4之后 Gp120区域，而Gag表位定位于12肽 在p27(aa281-292)中，这些表位是免疫优势的，就像原生CTL一样 裂解靶标呈现表位的程度可与 表达完整蛋白的靶点--单个NEF特异性CTL克隆 是从一种自然感染的煤烟山竹中分离出来的，20-mer AA21-40抗原表位图对这些动物的后续研究可能会揭示 病毒与CTL的相互作用导致非致病性SIV 感染