KIR2DL4Copy Number Variation Is Associated with CD4+T-Cell Depletion and Function of Cytokine-Producing NK Cell Subsets in SIV-InfectedMamu-A*01-Negative Rhesus Macaques

Hellmann, Ina; Letvin, Norman L.; Schmitz, Jörn E.

doi:10.1128/jvi.02949-12

Cited by 16 publications

(12 citation statements)

References 40 publications

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“…This could be a byproduct of ambiguous mapping of short reads onto larger exon contigs. However, this observation is consistent in rhesus macaques where Hellman et al (2013) found Mamu-KIR2DL4 copy numbers varied between one and three per cell. Understanding KIR2DL4 presence/absence and copy number variation requires sequencing of more animals to identify homozygous individuals with less common KIR haplotypes.…”

Section: Discussionsupporting

confidence: 81%

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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Section: Discussionsupporting

confidence: 81%

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

et al. 2017

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“…reported an association of high copy numbers of activating KIR3DS genes with lower peak viral load in animals negative for Mamu‐A1*001 and positive for a protective TRIM5 allele. In a further study, this group demonstrated high KIR2DL4 copy numbers to be associated with a better preservation of CD4 + T cells and an increased interferon‐ γ production of stimulated CD56 − CD16 − NK cells in SIV‐infected rhesus macaques . Albrecht et al .…”

Section: The Kir and Mhc Class I Gene Families Of Macaquesmentioning

confidence: 90%

Diversification of both KIR and NKG2 natural killer cell receptor genes in macaques – implications for highly complex MHC‐dependent regulation of natural killer cells

Walter

Petersen

2016

Immunology

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The killer immunoglobulin-like receptors (KIR) as well as their MHC class I ligands display enormous genetic diversity and polymorphism in macaque species. Signals resulting from interaction between KIR or CD94/NKG2 receptors and their cognate MHC class I proteins essentially regulate the activity of natural killer (NK) cells. Macaque and human KIR share many features, such as clonal expression patterns, gene copy number variations, specificity for particular MHC class I allotypes, or epistasis between KIR and MHC class I genes that influence susceptibility and resistance to immunodeficiency virus infection. In this review article we also annotated publicly available rhesus macaque BAC clone sequences and provide the first description of the CD94-NKG2 genomic region. Besides the presence of genes that are orthologous to human NKG2A and NKG2F, this region contains three NKG2C paralogues. Hence, the genome of rhesus macaques contains moderately expanded and diversified NKG2 genes in addition to highly diversified KIR genes. The presence of two diversified NK cell receptor families in one species has not been described before and is expected to require a complex MHC-dependent regulation of NK cells.

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“…For example, a recent study has shown strong association of activating receptor KIR2DL4 copy number with better CD4 ? T cells recovery in SIVinfected Mamu-A*01-negative rhesus macaques [106], suggesting KIR copy number is a strong protective determinant of the disease. In the same line, a genome-wide screening of structural variants has demonstrated association of high KIR3DS1 copy number with lower viral set point in the presence of a putative ligand, while NK cells from individual with high copy number of KIR3DL1 in the presence of KIR3DS1 and ligand show efficient inhibition of HIV-1 replication [107].…”

Section: Killer Cell Immunoglobulin (Ig)-like Receptors (Kirs)mentioning

confidence: 99%

Natural killer cell heterogeneity: cellular dysfunction and significance in HIV-1 immuno-pathogenesis

Ansari

Faried

Kamarulzaman

et al. 2015

Cell. Mol. Life Sci.

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Natural killer (NK) cells are innate immune effectors that provide first line of defence against viruses. Human NK cells are heterogeneous in nature, and their functions rely on a dynamic balance between germ-line-encoded activating and inhibitory receptors. HIV-1 infection results in altered NK cell receptor repertoire and impaired effector functions including the ability to lyse virus-infected cells and secretion of antiviral cytokine IFN-γ. Over the last decade, additional NK cell subset-specific molecules have been identified, leading to emergence of a more complex cellular diversity than previously thought. Herein, we discuss NK cell subset redistribution, altered receptor repertoire and influence of interaction of polymorphic leucocyte antigen (HLA) and killer cell immunoglobulin-like receptors (KIR) on HIV-1 disease progression.

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KIR2DL4Copy Number Variation Is Associated with CD4⁺T-Cell Depletion and Function of Cytokine-Producing NK Cell Subsets in SIV-InfectedMamu-A*01-Negative Rhesus Macaques

Cited by 16 publications

References 40 publications

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

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

Diversification of both KIR and NKG2 natural killer cell receptor genes in macaques – implications for highly complex MHC‐dependent regulation of natural killer cells

Natural killer cell heterogeneity: cellular dysfunction and significance in HIV-1 immuno-pathogenesis

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