Complete characterization of killer Ig-like receptor (KIR) haplotypes in Mauritian cynomolgus macaques: novel insights into nonhuman primate KIR gene content and organization - PubMed (original) (raw)

Comparative Study

Complete characterization of killer Ig-like receptor (KIR) haplotypes in Mauritian cynomolgus macaques: novel insights into nonhuman primate KIR gene content and organization

Benjamin N Bimber et al. J Immunol. 2008.

Abstract

Killer Ig-like receptors (KIRs) are implicated in protection from multiple pathogens including HIV, human papillomavirus, and malaria. Nonhuman primates such as rhesus and cynomolgus macaques are important models for the study of human pathogens; however, KIR genetics in nonhuman primates are poorly defined. Understanding KIR allelic diversity and genomic organization are essential prerequisites to evaluate NK cell responses in macaques. In this study, we present a complete characterization of KIRs in Mauritian cynomolgus macaques, a geographically isolated population. In this study we demonstrate that only eight KIR haplotypes are present in the entire population and characterize the gene content of each. Using the simplified genetics of this population, we construct a model for macaque KIR genomic organization, defining four putative KIR3DL loci, one KIR3DH, two KIR2DL, and one KIR1D. We further demonstrate that loci defined in Mauritian cynomolgus macaques can be applied to rhesus macaques. The findings from this study fundamentally advance our understanding of KIR genetics in nonhuman primates and establish a foundation from which to study KIR signaling in disease pathogenesis.

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Figures

FIGURE 1

FIGURE 1

Diagram of microsatellite markers. The diagram displays the position of microsatellite markers relative to published rhesus macaque KIR genes. Markers were designed using a complete haplotype sequenced by Sambrook et al. (35) (accession no. BX842591) and two genomic sequence contigs from the rhesus genome project (NW_001108469 and NW_001108471).

FIGURE 2

FIGURE 2

KIR haplotypes in MCM. A, The microsatellite profiles from the eight KIR haplotypes identified in MCM are shown. Marker name is indicated (left). Each column displays the size of the corresponding microsatellite repeat in base pairs. Null indicates lack of PCR amplification from a marker, suggestive of deletion within that haplotype. Several haplotypes contain multiple values for a microsatellite marker, suggesting duplication. Marker 374710-20138 was designed to amplify multiple microsatellites and therefore multiple allele sizes are expected. The order of markers was inferred using genomic sequence and segregation analysis. Markers within the centromeric and telomeric regions are indicated. B, The frequency of each haplotype within the MCM cohort is shown (n = 548 chromosomes). Recombinant haplotype (REC) is indicated. C, Shows the frequency of each KIR genotype within the population, expressed as the percentage within the 274 animal cohort. *, p < 0.05 for KIR genotypes with frequencies significantly lower than expected.

FIGURE 3

FIGURE 3

Phylogenetic analysis of MCM KIR3D sequences. A, The tree contains KIR3DL sequences. B, Shows KIR3DH sequences. Vertical bars indicate phylogenetic groups. The colors highlighting sequence names correspond to their haplotype.

FIGURE 4

FIGURE 4

Model for MCM KIR genomic organization. The gene organization is illustrated for the published rhesus macaque haplotype (top) and MCM haplotypes (bottom). MCM organization has been inferred using phylogenetic analysis. Loci have been named based on the closest rhesus macaque homolog. Where identified, pseudogenes are indicated (dotted box). Brackets indicate duplications of a locus. The linear order of loci within the telomeric region is arbitrary.

FIGURE 5

FIGURE 5

Phylogenetic tree of MCM and rhesus macaque KIR3DL sequences. MCM sequences are highlighted in gray; rhesus sequences are not highlighted. Phylogenetic groups are indicated (vertical bar).

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