MHC TYPING OF MACAQUES USED IN AIDS RESEARCH

用于艾滋病研究的猕猴 MHC 分型

• 批准号: 8173081
• 负责人: David I Watkins
• 金额: $ 5.16万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173081
• 关键词: Alleles; American; Animal Model; Ascaridil; Binding; CD8B1 gene; Cell Line; Characteristics; Chinese People; Communities; Computer Retrieval of Information on Scientific Projects Database; European; Funding; Genes; Genetic Polymorphism; Grant; HIV vaccine; HIV-1; HLA-B 2705 antigen; Haplotypes; Histocompatibility Antigens Class I; Immunogenetics; Immunologic Deficiency Syndromes; Individual; Infection; Institution; Laboratories; MHC Class I Genes; Macaca; Macaca fascicularis; Macaca mulatta; Membrane; Microsatellite Repeats; Molecular; Pan Genus; Pathogenesis; Peptides; Principal Investigator; Pseudogenes; Recording of previous events; Research; Research Personnel; Resources; SIV; Services; Shivering; Source; T-Lymphocyte; Techniques; Technology; Testing; Training; Transcript; United States National Institutes of Health; Vaccines; Variant; Virus; Virus Replication; Work; bean; neutralizing monoclonal antibodies; response; simian human immunodeficiency virus; vaccine development; virology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To offer MHC typing of the MHC class I and II loci for investigators working with macaques (Indian rhesus, Chinese rhesus, and Cynomolgus). To adapt technologies for HLA typing to molecular typing of macaque (Indian rhesus, Chinese rhesus, and Cynomolgus) MHC class I and II. The increased utility of various species of macaques as animal models in both HIV vaccine development and pathogenesis studies necessitates the continuation of reference MHC typing laboratories for these species. We plan to continue to offer services to both the North American and European scientific communities for MHC typing of macaques. Initially, this will include PCR-SSP tests for alleles encoding MHC class I and II molecules that bind peptides derived from SIV and SHIV. We are developing additional molecular techniques for analysis of the Indian rhesus and Chinese rhesus and Cynomolgus macaque MHC class I and class II alleles. Additionally, we offer training and materials to individual laboratories that wish to set up MHC typing. Finally, we are developing a panel of well-characterized cell lines that will be invaluable for the analysis of the MHC in the macaque. Since 2002 to the present, we have performed over 126,000 typings for over 130 investigators at 50 institutions. In 2009, we have conducted 21,800 typings at the request of 23 principal investigators from 19 different institutions. We are preparing to offer expanded Class II typing services during 2010. This research used WNPRC Immunogenetics & Virology Services. PUBLICATIONS: Doxiadis GG, Heijmans CM, Bonhomme M, Otting N, Crouau-Roy B, Bontrop RE. Compound evolutionary history of the rhesus macaque MHC class I B region revealed by microsatellite analysis and localization of retroviral sequences. PLoS One. 2009;4(1):e4287. PMID: 19172173 Wilson NA, Keele BF, Reed JS, Piaskowski SM, MacNair CE, Bett AJ, Liang X, Wang F, Thoryk E, Heidecker GJ, Citron MP, Huang L, Lin J, Vitelli S, Ahn CD, Kaizu M, Maness NJ, Reynolds MR, Friedrich TC, Loffredo JT, Rakasz EG, Erickson S, Allison DB, Piatak M Jr, Lifson JD, Shiver JW, Casimiro DR, Shaw GM, Hahn BH, Watkins DI. Vaccine-induced cellular responses control simian immunodeficiency virus replication after heterologous challenge. J Virol. 2009 Jul;83(13):6508-21. PMID: 19403685 Loffredo JT, Sidney J, Bean AT, Beal DR, Bardet W, Wahl A, Hawkins OE, Piaskowski S, Wilson NA, Hildebrand WH, Watkins DI, Sette A. Two MHC class I molecules associated with elite control of immunodeficiency virus replication, Mamu-B*08 and HLA-B*2705, bind peptides with sequence similarity. J Immunol. 2009 Jun 15;182(12):7763-75. PMID: 19494300 Valentine LE, Loffredo JT, Bean AT, Le¿n EJ, MacNair CE, Beal DR, Piaskowski SM, Klimentidis YC, Lank SM, Wiseman RW, Weinfurter JT, May GE, Rakasz EG, Wilson NA, Friedrich TC, O'Connor DH, Allison DB, Watkins DI. Infection with "escaped" virus variants impairs control of simian immunodeficiency virus SIVmac239 replication in Mamu-B*08-positive macaques. J Virol. 2009 Nov;83(22):11514-27. Sep 2.PMID: 19726517 Vojnov L, Reed JS, Weisgrau KL, Rakasz EG, Loffredo JT, Piaskowski SM, Sacha JB, Kolar HL, Wilson NA, Johnson RP, Watkins DI. Effective simian immunodeficiency virus-specific CD8+ T cells lack an easily detectable, shared characteristic. J Virol. 2010 Jan;84(2):753-64.PMID: 19889785 Otting N, Doxiadis GG, Bontrop RE. Definition of Mafa-A and -B haplotypes in pedigreed cynomolgus macaques (Macaca fascicularis). Immunogenetics. 2009 Nov 24. PMID: 19937015 de Groot NG, Heijmans CM, de Groot N, Doxiadis GG, Otting N, Bontrop RE. The chimpanzee Mhc-DRB region revisited: gene content, polymorphism, pseudogenes, and transcripts. Mol Immunol. 2009 Dec;47(2-3):381-9. PMID: 19800692 Hessell AJ, Rakasz EG, Tehrani DM, Huber M, Weisgrau KL, Landucci G, Forthal DN, Koff WC, Poignard P, Watkins DI, Burton DR. Broadly neutralizing monoclonal antibodies 2F5 and 4E10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus SHIVBa-L. J Virol. 2010 Feb;84(3):1302-13. PMID: 19906907

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 目的：为猕猴（印度恒河猴、中国恒河猴和食蟹猴）研究人员提供 MHC I 类和 II 类基因座的 MHC 分型。将 HLA 分型技术应用于猕猴（印度恒河猴、中国恒河猴和食蟹猴）MHC I 类和 II 类分子分型。 在 HIV 疫苗开发和发病机制研究中，各种猕猴作为动物模型的用途不断增加，因此有必要继续为这些物种建立参考 MHC 分型实验室。我们计划继续为北美和欧洲科学界提供猕猴 MHC 分型服务。最初，这将包括对编码 MHC I 类和 II 类分子的等位基因进行 PCR-SSP 测试，这些分子结合 SIV 和 SHIV 衍生的肽。我们正在开发其他分子技术来分析印度恒河猴、中国恒河猴和食蟹猴 MHC I 类和 II 类等位基因。此外，我们还为希望建立 MHC 分型的各个实验室提供培训和材料。最后，我们正在开发一组特征明确的细胞系，这对于分析猕猴的 MHC 非常有价值。自 2002 年至今，我们已为 50 个机构的 130 多名研究人员进行了 126,000 多次打字。 2009年，我们应来自19个不同机构的23名主要研究人员的要求进行了21,800次打字。我们准备在 2010 年期间提供扩展的 II 类打字服务。 这项研究使用了 WNPRC 免疫遗传学和病毒学服务。 出版物： Doxiadis GG、Heijmans CM、Bonhomme M、Otting N、Crouau-Roy B、Bontrop RE。通过微卫星分析和逆转录病毒序列定位揭示恒河猴 MHC I B 类区域的复合进化史。公共科学图书馆一号。 2009；4(1)：e4287。 PMID：19172173 Wilson NA、Keele BF、Reed JS、Piaskowski SM、MacNair CE、Bett AJ、Liang X、Wang F、Thoryk E、Heidecker GJ、Citron MP、Huang L、Lin J、Vitelli S、Ahn CD、Kaizu M、Maness NJ、Reynolds MR、Friedrich TC、Loffredo JT、Rakasz EG、Erickson S、Allison DB、Piatak M Jr、Lifson JD、Shiver JW、Casimiro DR、Shaw GM、Hahn BH、Watkins DI。疫苗诱导的细胞反应控制异源攻击后猿猴免疫缺陷病毒的复制。 J·维罗尔. 2009 年 7 月；83(13):6508-21。 PMID：19403685 Loffredo JT、Sidney J、Bean AT、Beal DR、Bardet W、Wahl A、Hawkins OE、Piaskowski S、Wilson NA、Hildebrand WH、Watkins DI、Sette A。与免疫缺陷病毒复制的精英控制相关的两种 MHC I 类分子 Mamu-B*08 和 HLA-B*2705 与具有序列相似性的肽结合。 J免疫学杂志。 2009 年 6 月 15 日；182(12)：7763-75。 PMID：19494300 Valentine LE、Loffredo JT、Bean AT、Le¿n EJ、MacNair CE、Beal DR、Piaskowski SM、Klimentidis YC、Lank SM、Wiseman RW、Weinfurter JT、May GE、Rakasz EG、Wilson NA、Friedrich TC、O'Connor DH、Allison DB、Watkins DI。 “逃逸”病毒变体的感染会损害 Mamu-B*08 阳性猕猴中对猿猴免疫缺陷病毒 SIVmac239 复制的控制。 J·维罗尔. 2009 年 11 月；83(22)：11514-27。 9月2日PMID：19726517 Vojnov L、Reed JS、Weisgrau KL、Rakasz EG、Loffredo JT、Piaskowski SM、Sacha JB、Kolar HL、Wilson NA、Johnson RP、Watkins DI。有效的猿猴免疫缺陷病毒特异性 CD8+ T 细胞缺乏易于检测的共同特征。 J·维罗尔. 2010年1月;84(2):753-64.PMID: 19889785 奥廷 N、Doxiadis GG、Bontrop RE。 纯种食蟹猴 (Macaca fascicularis) 中 Mafa-A 和 -B 单倍型的定义。免疫遗传学。 2009 年 11 月 24 日。PMID：19937015 de Groot NG、Heijmans CM、de Groot N、Doxiadis GG、Otting N、Bontrop RE。 黑猩猩 Mhc-DRB 区域重温：基因内容、多态性、假基因和转录本。分子免疫学。 2009 年 12 月；47(2-3):381-9。 PMID：19800692 Hessel AJ、Rakasz EG、Tehrani DM、Huber M、Weisgrau KL、Landucci G、Forthal DN、Koff WC、Poignard P、Watkins DI、Burton DR。针对人类免疫缺陷病毒 1 型 gp41 膜近外部区域的广泛中和单克隆抗体 2F5 和 4E10 可保护免受猿猴人类免疫缺陷病毒 SHIVBa-L 的粘膜攻击。 J·维罗尔. 2010 年 2 月；84(3)：1302-13。 PMID：19906907