Major histocompatibility complex haplotyping and long-amplicon allele discovery in cynomolgus macaques from Chinese breeding facilities

Karl, Julie A.; Graham, Michael E.; Wiseman, Roger W.; Heimbruch, Katelyn E.; Gieger, Samantha M.; Doxiadis, Gaby G. M.; Bontrop, Ronald E.; O’Connor, David H.

doi:10.1007/s00251-017-0969-7

Cited by 42 publications

(70 citation statements)

References 33 publications

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“…An amplicon library was created by the addition of SMRTbell adaptors according to manufacturer’s protocols and subjected to circular consensus sequencing on a PacBio RSII instrument (Pacific Biosciences). The resulting sequences were analyzed as described recently by Karl et al (48) using a series of open-source bioinformatics tools and the Geneious Pro v9.1.7 software (Biomatters Ltd.). 454 MHC-E typing of 51 rhesus macaques was performed as previously described for MHC-I (41).…”

Section: Methodsmentioning

confidence: 99%

The Role of MHC-E in T Cell Immunity Is Conserved among Humans, Rhesus Macaques, and Cynomolgus Macaques

Wiseman

Hughes

et al. 2018

The Journal of Immunology

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Major histocompatibility complex E (MHC-E) is a highly conserved non-classical MHC-Ib molecule that predominantly binds and presents MHC-Ia leader sequence-derived peptides for natural killer cell regulation. However, MHC-E also binds pathogen-derived peptide antigens for presentation to CD8+ T cells. Given this role in adaptive immunity and its highly monomorphic nature in the human population, HLA-E is an attractive target for novel vaccine and immunotherapeutic modalities. Development of HLA-E-targeted therapies will require a physiologically relevant animal model that recapitulates HLA-E-restricted T cell biology. Here, we investigated MHC-E immunobiology in two common nonhuman primate species, Indian-origin rhesus macaques (RM) and Mauritian-origin cynomolgus macaques (MCM). Compared to humans and MCM, RM expressed a greater number of MHC-E alleles at both the population and individual level. Despite this difference, human, RM, and MCM MHC-E molecules were expressed at similar levels across immune cell subsets, equivalently up-regulated by viral pathogens, and bound and presented identical peptides to CD8+ T cells. Indeed, SIV-specific, Mamu-E-restricted CD8+ T cells from RM recognized antigenic peptides presented by all MHC-E molecules tested, including cross-species recognition of human and MCM SIV-infected CD4+ T cells. Thus, MHC-E is functionally conserved among humans, RM, and MCM, and both RM and MCM represent physiologically relevant animal models of HLA-E-restricted T cell immunobiology.

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Section: Methodsmentioning

confidence: 99%

The Role of MHC-E in T Cell Immunity Is Conserved among Humans, Rhesus Macaques, and Cynomolgus Macaques

Wiseman

Hughes

et al. 2018

The Journal of Immunology

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“…The Pacific Biosciences RS II system (Menlo Park, CA, USA) protocols for single-molecule real-time (SMRT) circular consensus sequencing (CCS) of MHC class I full-length transcript amplicons were followed as previously described (Karl et al 2017; Westbrook et al 2015). The 24 samples selected for sequencing were processed in three separate pools of eight samples each, with a mixture of two and three different 5′ and 3′ primers, respectively (Suppl.…”

Section: Methodsmentioning

confidence: 99%

“…Reads of 900–1200 bp were extracted from the pre-processed reads of insert files (Karl et al 2017) (www.pacb.com). …”

Section: Methodsmentioning

confidence: 99%

“…Putative novel sequences and extensions of known transcripts were manually validated using Geneious Pro (version 9.0) (Karl et al 2017). All novel and extension sequences supported by three or more perfectly identical full-length reads were submitted to the NCBI GenBank for accession numbers, and to the Immuno Polymorphism Database for the Major Histocompatibility Complex genes of Non-Human Primates (IPD-MHC NHP) (http://www.ebi.ac.uk/ipd/mhc/nhp/index.html) for official nomenclature (de Groot et al 2012; Maccari et al 2017) (Suppl.…”

Section: Methodsmentioning

confidence: 99%

“…The B region in macaques shows even more CNV, and up to seven major and eight minor genes may be defined per haplotype. In contrast to the A region, however, a clear differentiation between major and minor B genes is difficult, as well as a definitive allocation of alleles to a certain locus (Budde et al 2010; Doxiadis et al 2011, 2013; Fernandez et al 2011; Karl et al 2013, 2017; Naruse et al 2010; O’Leary et al 2009; Otting et al 2005, 2007, 2009, 2012; Saito et al 2012; Shiina et al 2015). …”

Section: Introductionmentioning

confidence: 99%

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MHC class I diversity of olive baboons (Papio anubis) unravelled by next-generation sequencing

et al. 2018

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The olive baboon represents an important model system to study various aspects of human biology and health, including the origin and diversity of the major histocompatibility complex. After screening of a group of related animals for polymorphisms associated with a well-defined microsatellite marker, subsequent MHC class I typing of a selected population of 24 animals was performed on two distinct next-generation sequencing (NGS) platforms. A substantial number of 21 A and 80 B transcripts were discovered, about half of which had not been previously reported. Per animal, from one to four highly transcribed A alleles (majors) were observed, in addition to ones characterised by low transcripion levels (minors), such as members of the A*14 lineage. Furthermore, in one animal, up to 13 B alleles with differential transcription level profiles may be present. Based on segregation profiles, 16 Paan-AB haplotypes were defined. A haplotype encodes in general one or two major A and three to seven B transcripts, respectively. A further peculiarity is the presence of at least one copy of a B*02 lineage on nearly every haplotype, which indicates that B*02 represents a separate locus with probably a specialistic function. Haplotypes appear to be generated by recombination-like events, and the breakpoints map not only between the A and B regions but also within the B region itself. Therefore, the genetic makeup of the olive baboon MHC class I region appears to have been subject to a similar or even more complex expansion process than the one documented for macaque species.Electronic supplementary materialThe online version of this article (10.1007/s00251-018-1053-7) contains supplementary material, which is available to authorized users.

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Improved full-length killer cell immunoglobulin-like receptor transcript discovery in Mauritian cynomolgus macaques

et al. 2017

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Killer cell Immunoglobulin-like Receptors (KIRs) modulate disease progression of pathogens including HIV, malaria, and hepatitis C. Cynomolgus and rhesus macaques are widely used as nonhuman primate models to study human pathogens and so considerable effort has been put into characterizing their KIR genetics. However, previous studies have relied on cDNA cloning and Sanger sequencing that lacks the throughput of current sequencing platforms. In this study, we present a high throughput, full-length allele discovery method utilizing PacBio circular consensus sequencing (CCS). We also describe a new approach to Macaque Exome Sequencing (MES) and the development of the Rhexome1.0, an adapted target capture reagent that includes macaque-specific capture probesets. By using sequence reads generated by whole genome sequencing (WGS) and MES to inform primer design, we were able to increase the sensitivity of KIR allele discovery. We demonstrate this increased sensitivity by defining nine novel alleles within a cohort of Mauritian cynomolgus macaques (MCM), a geographically isolated population with restricted KIR genetics that was thought to be completely characterized. Finally, we describe an approach to genotyping KIRs directly from sequence reads generated using WGS/MES reads. The findings presented here expand our understanding of KIR genetics in MCM by associating new genes with all eight KIR haplotypes and demonstrating the existence of at least one KIR3DS gene associated with every haplotype.

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Major histocompatibility complex haplotyping and long-amplicon allele discovery in cynomolgus macaques from Chinese breeding facilities

Cited by 42 publications

References 33 publications

The Role of MHC-E in T Cell Immunity Is Conserved among Humans, Rhesus Macaques, and Cynomolgus Macaques

The Role of MHC-E in T Cell Immunity Is Conserved among Humans, Rhesus Macaques, and Cynomolgus Macaques

MHC class I diversity of olive baboons (Papio anubis) unravelled by next-generation sequencing

Improved full-length killer cell immunoglobulin-like receptor transcript discovery in Mauritian cynomolgus macaques

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