YEARS

2005-2017

AUTHORS

Bianca Romina Mothe

TITLE

MHC characterization in Chinese rhesus macaques

ABSTRACT

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.

FUNDED PUBLICATIONS

  • SIV-infected Chinese-origin rhesus macaques express specific MHC class I alleles in either elite controllers or normal progressors.
  • Peptide-binding motifs associated with MHC molecules common in Chinese rhesus macaques are analogous to those of human HLA supertypes and include HLA-B27-like alleles
  • A shared MHC supertype motif emerges by convergent evolution in macaques and mice, but is totally absent in human MHC molecules.
  • 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
  • Peptide-binding motifs associated with MHC molecules common in Chinese rhesus macaques are analogous to those of human HLA supertypes and include HLA-B27-like alleles.
  • The most common Chinese rhesus macaque MHC class I molecule shares peptide binding repertoire with the HLA-B7 supertype.
  • The most common Chinese rhesus macaque MHC class I molecule shares peptide binding repertoire with the HLA-B7 supertype
  • Diverse recognition of conserved orthopoxvirus CD8+ T cell epitopes in vaccinated rhesus macaques.
  • 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.
  • A shared MHC supertype motif emerges by convergent evolution in macaques and mice, but is totally absent in human MHC molecules
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    27 TRIPLES      17 PREDICATES      28 URIs      9 LITERALS

    Subject Predicate Object
    1 grants:c26d8703fd7428ff75d5638088793de2 sg:abstract 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.
    2 sg:endYear 2017
    3 sg:fundingAmount 789450.0
    4 sg:fundingCurrency USD
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    19 sg:hasRecipientOrganization grid-institutes:grid.253566.1
    20 sg:language English
    21 sg:license http://scigraph.springernature.com/explorer/license/
    22 sg:scigraphId c26d8703fd7428ff75d5638088793de2
    23 sg:startYear 2005
    24 sg:title MHC characterization in Chinese rhesus macaques
    25 sg:webpage http://projectreporter.nih.gov/project_info_description.cfm?aid=8541665
    26 rdf:type sg:Grant
    27 rdfs:label Grant: MHC characterization in Chinese rhesus macaques
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