MHC characterization in Chinese rhesus macaques

中国恒河猴 MHC 特征

• 批准号: 8541665
• 负责人: Bianca Romina Mothe
• 金额: $ 37万
• 依托单位: CALIFORNIA STATE UNIVERSITY SAN MARCOS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-15 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8541665
• 关键词: Acquired Immunodeficiency Syndrome; Alleles; Animals; Binding; Biological Assay; California; Cells; Chinese People; Data; Dideoxy Chain Termination DNA Sequencing; Epitopes; Exposure to; Gene Frequency; Goals; Grant; HLA-A2 Antigen; HLA-A3 Antigen; HLA-B7 Antigen; Human; Immune response; Immunogenetics; Immunologic Markers; In Vitro; Infection; Laboratories; Learning; Macaca; Macaca mulatta; Major Histocompatibility Complex; Manuscripts; Methods; Modeling; Paper; Peptides; Peripheral Blood Mononuclear Cell; Primates; Process; Publications; Research; Research Personnel; SIV; Scientist; Students; Technology; Testing; Training; Universities; Vaccines; Washington; Work; Writing; base; cross reactivity; design; enzyme linked immunospot assay; interest; new technology; next generation sequencing; nonhuman primate; public health relevance; research study

DESCRIPTION (provided by applicant): We will determine if HLA analogy extends to cellular reactivity by testing cells from AIDS- infected Chinese rhesus macaques expressing specific alleles of interest. We will also identify MHC alleles that are common in a set of infected animals and characterize them to identify SIV-specific epitopes. We propose to expand and continue the work we performed in our previous AREA grant. In the original grant, we characterized rhesus macaques based on the definition of MHC-peptide binding motifs, data from in vitro MHC-peptide binding assays, and have identified sets of analogous MHC molecules in humans and rhesus macaques. Analogous MHC molecules are defined as MHC molecules associated with a high degree of interspecies cross-reactivity (largely overlapping peptide binding repertoires). We now propose to advance these analyses using new technology consisting of next generation sequencing, to identify MHC molecules in a set of SIV-infected Chinese rhesus macaques. We will determine if HLA analogy extends to cellular reactivity by testing cells from SIV- infected Chinese rhesus macaques expressing specific alleles of interest. Furthermore, we will identify MHC alleles that are common in these infected animals and characterize them to identify SIV- specific epitopes. Our goal is also to understand HLA analogy from a functional perspective as well as identify any new commonly expressed MHC class I alleles. Accordingly, we propose the following specific aims: 1) To identify the complete set of MHC class I alleles in a set of SIVmac239- infected Chinese rhesus macaques using next generation sequencing. 2) To characterize MHC:peptide binding motifs and associated functional immune responses specific in Chinese rhesus macaques. Fifty-six Chinese rhesus macaques are being studied as part of a vaccine study at Washington National Primate Center. We already have preliminary MHC data on a subset of these animals as part of our previous AREA grant. These studies were performed using traditional Sanger sequencing methods. We will now expand the MHC typing of these efforts using next generation sequencing on the [MiSeq platform]. Upon MHC identification of these 56 animals, we will perform additional studies to characterize cellular immune responses. We will receive PBMC which we will use to analyze immune responses. From these data, we will be able to determine cellular reactivity in the context of analogous MHC alleles in Chinese rhesus macaque to HLA alleles and whether there are additional high frequency alleles.

描述（由申请人提供）：我们将通过检测来自表达感兴趣的特定等位基因的AIDS感染的中国恒河猴的细胞来确定HLA类似物是否延伸到细胞反应性。我们还将确定在一组受感染动物中常见的MHC等位基因 并对其进行表征以鉴定SIV特异性表位。我们建议扩大和继续我们在以前的地区赠款中所做的工作。在最初的授权中，我们根据MHC-肽结合基序的定义，体外MHC-肽结合测定的数据表征了恒河猴，并在人类和恒河猴中鉴定了类似的MHC分子。类似MHC分子定义为与高度种间交叉反应性相关的MHC分子（大部分重叠肽结合库）。 我们现在建议使用新技术，包括下一代测序，以确定在一组SIV感染的中国恒河猴的MHC分子，以推进这些分析。我们将通过检测SIV感染的中国恒河猴表达感兴趣的特定等位基因的细胞来确定HLA类似性是否延伸到细胞反应性。此外，我们将鉴定这些感染动物中常见的MHC等位基因，并对其进行表征以鉴定SIV特异性表位。我们的目标也是从功能的角度来理解HLA的相似性，以及确定任何新的常见表达的MHC I类等位基因。因此，我们提出了以下具体目标：1）使用下一代测序技术鉴定一组SIVmac 239感染的中国恒河猴中的完整的MHC I类等位基因组。2)研究中国恒河猴主要组织相容性复合体（MHC）多肽结合基序及其相关的功能性免疫反应。 华盛顿国家灵长类动物中心正在对五十六只中国恒河猴进行疫苗研究。我们已经有了这些动物的一个子集的初步MHC数据，作为我们以前的区域赠款的一部分。这些研究使用传统的桑格测序方法进行。我们现在将在[MiSeq平台]上使用下一代测序来扩展这些工作的MHC分型。在对这56只动物进行MHC鉴定后，我们将进行额外的研究以表征细胞免疫应答。我们将接受PBMC，我们将使用它来分析免疫应答。从这些数据中，我们将能够确定在中国恒河猴中类似的MHC等位基因的背景下，HLA等位基因的细胞反应性，以及是否有额外的高频等位基因。

项目成果

SIV-infected Chinese-origin rhesus macaques express specific MHC class I alleles in either elite controllers or normal progressors.

• DOI: 10.1111/j.1600-0684.2011.00487.x
• 发表时间: 2011-08
• 期刊: Journal of medical primatology
• 影响因子: 0.7
• 作者: Wambua D;Henderson R;Solomon C;Hunter M;Marx P;Sette A;Mothé BR
• 通讯作者: Mothé BR

The most common Chinese rhesus macaque MHC class I molecule shares peptide binding repertoire with the HLA-B7 supertype.

• DOI: 10.1007/s00251-010-0450-3
• 发表时间: 2010-07
• 期刊: IMMUNOGENETICS
• 影响因子: 3.2
• 作者: Solomon, Christopher;Southwood, Scott;Hoof, Ilka;Rudersdorf, Richard;Peters, Bjoern;Sidney, John;Pinilla, Clemencia;Marcondes, Maria Cecilia Garibaldi;Ling, Binhua;Marx, Preston;Sette, Alessandro;Mothe, Bianca R.
• 通讯作者: Mothe, Bianca R.

Functional analysis of frequently expressed Chinese rhesus macaque MHC class I molecules Mamu-A1*02601 and Mamu-B*08301 reveals HLA-A2 and HLA-A3 supertypic specificities.

• DOI: 10.1007/s00251-010-0502-8
• 发表时间: 2011-05
• 期刊: IMMUNOGENETICS
• 影响因子: 3.2
• 作者: Southwood, Scott;Solomon, Christopher;Hoof, Ilka;Rudersdorf, Richard;Sidney, John;Peters, Bjoern;Wahl, Angela;Hawkins, Oriana;Hildebrand, William;Mothe, Bianca R.;Sette, Alessandro
• 通讯作者: Sette, Alessandro