KIR3DL01 Recognition of Bw4 Ligands in the Rhesus Macaque: Maintenance of Bw4 Specificity since the Divergence of Apes and Old World Monkeys

Schafer, Jamie L.; Colantonio, Arnaud D.; Neidermyer, William J.; Dudley, Dawn M.; Connole, Michelle; O’Connor, David H.; Evans, David T.

doi:10.4049/jimmunol.1302883

Cited by 29 publications

(61 citation statements)

References 52 publications

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“…In comparison to human inhibitory KIR (iKIR), the iKIR–MHC class I interactions in macaques are characterized by lower avidity and broader reactivity . Although the Bw4/Bw6 motifs play a role in binding macaque KIR3D proteins, there are some KIR3D with restricted specificity for Bw4 such as KIR3DL01 or KIR3DLW03, whereas other iKIR bind to both motifs such as KIR3DL05 or KIR049‐4 . One reason for this broader reactivity of some iKIR might be the enormous genetic diversity and copy number variation in macaque species that might favour the evolution of KIR with broad interaction specificity.…”

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

confidence: 99%

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

confidence: 99%

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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“…Although rhesus KIR3DL01 and human KIR3DL1 are not orthologous, they may have similar functions; both recognize Bw4 ligands and are the most polymorphic KIRs of their respective species [29]. Moreover, the lysis of HIV-infected cells by KIR3DL1 + NK cells is primarily triggered by downmodulation of HLA-Bw4 ligands from the cell surface by the viral Nef protein [8,22], and we previously demonstrated that Mamu-Bw4 molecules are efficiently downmodulated by SIV Nef [65].…”

Section: Discussionmentioning

confidence: 99%

KIR3DL01 upregulation on gut natural killer cells in response to SIV infection of KIR- and MHC class I-defined rhesus macaques

et al. 2017

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Natural killer cells provide an important early defense against viral pathogens and are regulated in part by interactions between highly polymorphic killer-cell immunoglobulin-like receptors (KIRs) on NK cells and their MHC class I ligands on target cells. We previously identified MHC class I ligands for two rhesus macaque KIRs: KIR3DL01 recognizes Mamu-Bw4 molecules and KIR3DL05 recognizes Mamu-A1*002. To determine how these interactions influence NK cell responses, we infected KIR3DL01+ and KIR3DL05+ macaques with and without defined ligands for these receptors with SIVmac239, and monitored NK cell responses in peripheral blood and lymphoid tissues. NK cell responses in blood were broadly stimulated, as indicated by rapid increases in the CD16+ population during acute infection and sustained increases in the CD16+ and CD16-CD56- populations during chronic infection. Markers of proliferation (Ki-67), activation (CD69 & HLA-DR) and antiviral activity (CD107a & TNFα) were also widely expressed, but began to diverge during chronic infection, as reflected by sustained CD107a and TNFα upregulation by KIR3DL01+, but not by KIR3DL05+ NK cells. Significant increases in the frequency of KIR3DL01+ (but not KIR3DL05+) NK cells were also observed in tissues, particularly in the gut-associated lymphoid tissues, where this receptor was preferentially upregulated on CD56+ and CD16-CD56- subsets. These results reveal broad NK cell activation and dynamic changes in the phenotypic properties of NK cells in response to SIV infection, including the enrichment of KIR3DL01+ NK cells in tissues that support high levels of virus replication.

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“…Glu76 has also been shown to play a role in regulating KIR interactions with the Bw4 motif in non-human primates (39). Interestingly, in contrast to human KIR3DL1*001, recognition of Bw4 allotypes by Mamu-KIR3DL01 was impaired by the presence of a glutamate at position 76.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, in contrast to human KIR3DL1*001, recognition of Bw4 allotypes by Mamu-KIR3DL01 was impaired by the presence of a glutamate at position 76. Indeed ligands for Mamu-KIR3DL01 such as Mamu-B*65:01, have a glycine at this position and mutation to glutamate impaired recognition (39). It is nevertheless unclear whether this inability to tolerate a glutamate at position 76 stems from an altered positioning of the side chain relative to human Bw4 allotypes or that the mode of ligand recognition differs between Mamu-KIR3DL01 and KIR3DL1*001.…”

Section: Discussionmentioning

confidence: 99%

The Interaction of KIR3DL1*001 with HLA Class I Molecules Is Dependent upon Molecular Microarchitecture within the Bw4 Epitope

Saunders

Vivian

Baschuk

et al. 2015

The Journal of Immunology

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The Killer cell Immunoglobulin-like Receptor 3DL1 (KIR3DL1) inhibits activation of Natural Killer (NK) cells upon interaction with Human Leukocyte Antigen (HLA) class I molecules such as HLA-B*57:01 which contain the Bw4 epitope spanning residues 77-83 (e.g. NLRIALR) and not with HLA allomorphs that possess the Bw6 motif (e.g. HLA-B*08:01), which differ at residues 77, 80, 81, 82 and 83. Although Bw4 residues Ile80 and Arg83 directly interact with KIR3DL1*001, their precise role in determining KIR3DL1-HLA-Bw4 specificity remains unclear. Recognition of HLA-B*57:01 by either KIR3DL1+ NK cells or the NK cell line YTS transfected with KIR3DL1*001 was impaired by mutation of residues 80 and 83 of HLA-B*57:01 to the corresponding amino acids within the Bw6 motif. Conversely, the simultaneous introduction of three Bw4 residues at positions 80, 82 and 83 into HLA-B*08:01 conferred an interaction with KIR3DL1*001. Structural analysis of HLA-B*57:01, HLA-B*08:01 and mutants of each bearing substitutions at positions 80 and 83 revealed that Ile80 and Arg83 within the Bw4 motif constrain the conformation of Glu76, primarily through a salt-bridge between Arg83 and Glu76. This salt-bridge was absent in HLA-Bw6 molecules as well as position 83 mutants of HLA-B*57:01. Mutation of the Bw4 residue Ile80 also disrupted this salt-bridge, providing further insight into the role that position 80 plays in mediating KIR3DL1 recognition. Thus the strict conformation of HLA-Bw4 allotypes, held in place by the Glu76-Arg83 interaction, facilitates KIR3DL1 binding whereas Bw6 allotypes present a platform on the α1 helix that is less permissive for KIR3DL1 binding.

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KIR3DL01 Recognition of Bw4 Ligands in the Rhesus Macaque: Maintenance of Bw4 Specificity since the Divergence of Apes and Old World Monkeys

Cited by 29 publications

References 52 publications

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

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

KIR3DL01 upregulation on gut natural killer cells in response to SIV infection of KIR- and MHC class I-defined rhesus macaques

The Interaction of KIR3DL1*001 with HLA Class I Molecules Is Dependent upon Molecular Microarchitecture within the Bw4 Epitope

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