Activating killer cell immunoglobulin-like receptor 2DS2 binds to HLA-A*11

Liu, Jingxian; Xiao, Ziwei; Ko, Hui Ling; Shen, Meixin; Ren, Ee Chee

doi:10.1073/pnas.1322052111

Cited by 76 publications

(88 citation statements)

References 31 publications

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“…HLA-A*11:01 was recently identified as a ligand for KIR2DS2 (30). Despite the absence of the HLA-A*11:01 gene on the genotype of the P3, 2012-018, and 2011-20-I cells (Table II, Supplemental Table II), NK cells from donors with a KIR2DS2 + genotype killed P3 and 2012-018 cells more efficiently than did NK cells from donors without the KIR2DS2 gene (Fig.…”

Section: Kir2ds2 Immunogenotype Confers a Functional Activation Advanmentioning

confidence: 92%

NK Cells with KIR2DS2 Immunogenotype Have a Functional Activation Advantage To Efficiently Kill Glioblastoma and Prolong Animal Survival

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Kmiecik

Leiss

et al. 2014

The Journal of Immunology

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Glioblastomas (GBMs) are lethal brain cancers that are resistant to current therapies. We investigated the cytotoxicity of human allogeneic NK cells against patient-derived GBM in vitro and in vivo, as well as mechanisms mediating their efficacy. We demonstrate that KIR2DS2 immunogenotype NK cells were more potent killers, notwithstanding the absence of inhibitory killer Ig–like receptor (KIR)-HLA ligand mismatch. FACS-sorted and enriched KIR2DS2+ NK cell subpopulations retained significantly high levels of CD69 and CD16 when in contact with GBM cells at a 1:1 ratio and highly expressed CD107a and secreted more soluble CD137 and granzyme A. In contrast, KIR2DS2− immunogenotype donor NK cells were less cytotoxic against GBM and K562, and, similar to FACS-sorted or gated KIR2DS2− NK cells, significantly diminished CD16, CD107a, granzyme A, and CD69 when in contact with GBM cells. Furthermore, NK cell–mediated GBM killing in vitro depended upon the expression of ligands for the activating receptor NKG2D and was partially abrogated by Ab blockade. Treatment of GBM xenografts in NOD/SCID mice with NK cells from a KIR2DS2+ donor lacking inhibitory KIR-HLA ligand mismatch significantly prolonged the median survival to 163 d compared with vehicle controls (log-rank test, p = 0.0001), in contrast to 117.5 d (log-rank test, p = 0.0005) for NK cells with several inhibitory KIR-HLA ligand mismatches but lacking KIR2DS2 genotype. Significantly more CD56+CD16+ NK cells from a KIR2DS2+ donor survived in nontumor-bearing brains 3 wk after infusion compared with KIR2DS2− NK cells, independent of their proliferative capacity. In conclusion, KIR2DS2 identifies potent alloreactive NK cells against GBM that are mediated by commensurate, but dominant, activating signals.

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Section: Kir2ds2 Immunogenotype Confers a Functional Activation Advanmentioning

confidence: 92%

NK Cells with KIR2DS2 Immunogenotype Have a Functional Activation Advantage To Efficiently Kill Glioblastoma and Prolong Animal Survival

Navarro

Kmiecik

Leiss

et al. 2014

The Journal of Immunology

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“…3F and 3G). In order to generate a positive control peptide for this experiment, we tested P7 and P8 derivatives of the naturally processed HLA-C*0304-binding peptide, GAVDPLLAL, guided by our current work and also that of Liu et al (13,24). GAVDPLLAL, GAVDPLAWL and GAVDPLATL all stabilised HLA-C*0304, but only GAVDPLAWL induced binding of the KIR2DS2 tetramer to HLA-C*0304 and Vav1 phosphorylation ( Fig.…”

Section: Kir2ds2 Recognizes Lnpsvaatl In the Context Of Hcv Infectionmentioning

confidence: 99%

KIR2DS2 recognizes conserved peptides derived from viral helicases in the context of HLA-C

et al. 2017

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This is the author accepted manuscript (AAM). The final published version (version of record) is available online via AAAS at http://immunology.sciencemag.org/content/2/15/eaal5296. Please refer to any applicable terms of use of the publisher. University of Bristol -Explore Bristol Research General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. KIR2DS2, an activating natural killer cell receptor recognizes highly conserved peptides derived from the RNA helicases of pathogenic flaviviruses. AbstractKiller cell immunoglobulin-like receptors (KIR) are rapidly evolving species-specific natural killer cell receptors associated with protection against multiple different human viral infections. We report that the activating receptor KIR2DS2 directly recognizes viral peptides derived from conserved regions of flaviviral superfamily 2 RNA helicases in the context of MHC class I. The peptide LNPSVAATL, from the HCV helicase, binds HLA-C*0102 leading to NK cell activation through engagement of KIR2DS2. Similarly, HLA-C*0102 presents highly conserved peptides from the helicase motif 1b region of related flaviviruses, including dengue, Zika, yellow fever and Japanese encephalitis viruses, to KIR2DS2. These flaviviral peptides all contain an "MCHAT" motif, which is present in 61 out of 63 flaviviruses.LNPSVAATL is also highly conserved across HCV genotypes and mutation of this epitope is poorly tolerated by HCV. KIR2DS2 recognizes endogenously presented helicase peptides and KIR2DS2 is sufficient to inhibit HCV and dengue virus replication in the context of HLA-C*0102. Targeting short, but highly conserved, viral peptides provide non-rearranging innate immune receptors with an efficient mechanism to recognize multiple, highly variable pathogenic RNA viruses.4

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“…Three key advancements have progressed understanding of the recognition of HLA class I by KIR; (i) the crystal structures of KIR in complex with their HLA class I ligands,10, 35, 70, 99 (ii) the development of soluble KIR36, 100, 101 and (iii) their use in a multiplex immunoassay against a broad panel of HLA class I allotypes102, 103 (Fig. 3).…”

Section: Kir Ligand Bindingmentioning

confidence: 99%

“…The binding motifs are referred to as C1 and C2 in HLA ‐C and Bw4 in HLA ‐B and HLA ‐A. The precise KIR binding motif of HLA ‐A*11, which can be recognized by KIR 2 DS 2, KIR 2 DS 4 and KIR 3 DL 2, has not been determined 10, 11. Interactions may also be sensitive to polymorphism outside the HLA and KIR binding motifs and to the presented peptide sequence.…”

Section: Introductionmentioning

confidence: 99%

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

et al. 2016

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SummaryKiller‐cell immunoglobulin‐like receptors (KIRs) are components of two fundamental biological systems essential for human health and survival. First, they contribute to host immune responses, both innate and adaptive, through their expression by natural killer cells and T cells. Second, KIR play a key role in regulating placentation, and hence reproductive success. Analogous to the diversity of their human leucocyte antigen class I ligands, KIR are extremely polymorphic. In this review, we describe recent developments, fuelled by methodological advances, that are helping to decipher the KIR system in terms of haplotypes, polymorphisms, expression patterns and their ligand interactions. These developments are delivering deeper insight into the relevance of KIR in immune system function, evolution and disease.

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Activating killer cell immunoglobulin-like receptor 2DS2 binds to HLA-A*11

Cited by 76 publications

References 31 publications

NK Cells with KIR2DS2 Immunogenotype Have a Functional Activation Advantage To Efficiently Kill Glioblastoma and Prolong Animal Survival

NK Cells with KIR2DS2 Immunogenotype Have a Functional Activation Advantage To Efficiently Kill Glioblastoma and Prolong Animal Survival

KIR2DS2 recognizes conserved peptides derived from viral helicases in the context of HLA-C

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

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