HIV Protective <i>KIR3DL1</i> and <i>HLA-B</i> Genotypes Influence NK Cell Function Following Stimulation with HLA-Devoid Cells

Boulet, Salix; Song, Rujun; Kamya, Philomena; Bruneau, Julie; Shoukry, Naglaa H.; Tsoukas, Christos; Bernard, Nicole F.

doi:10.4049/jimmunol.0902621

Cited by 90 publications

(104 citation statements)

References 57 publications

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“…This possibility is concordant with the epidemiological observation that SPs have higher frequencies of inhibitory KIR3DL1/HLA-Bw4 ligand combinations than do individuals with more rapidly progressing infections (45). It was demonstrated that these KIR/HLA combinations increase the functional potential of NK cells during the ontological process of NK cell education (46,47) and that this education results in higher anti-HIV ADCC against autologous targets (48). Furthermore, an additional study (49) demonstrated that NK cells carrying KIR3DL1 are expanded in primary HIV infection.…”

Section: Discussionsupporting

confidence: 75%

Anti-HIV Antibody–Dependent Activation of NK Cells Impairs NKp46 Expression

Parsons

Tang

Jegaskanda

et al. 2014

The Journal of Immunology

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There is much interest in the potential of Ab-dependent cellular cytotoxicity (ADCC) to slow disease progression following HIV infection. Despite several studies demonstrating a positive association between ADCC and slower disease progression, it is possible that continued stimulation of NK cells by ADCC during chronic HIV infection could render these cells dysfunctional. Indeed, activation of NK cells by ADCC results in matrix metalloproteinase–induced reductions in CD16 expression and activation refractory periods. In addition, ex vivo analyses of NK cells from HIV-infected individuals revealed other alterations in phenotype, such as decreased expression of the activating NKp46 receptor that is essential for NK-mediated antitumor responses and immunity from infection. Because NKp46 shares a signaling pathway with CD16, we hypothesized that activation-induced downregulation of both receptors could be controlled by a common mechanism. We found that activation of NK cells by anti-HIV or anti-CD16 Abs resulted in NKp46 downregulation. The addition of a matrix metalloproteinase inhibitor attenuated NKp46 downregulation following NK cell activation by anti-HIV Abs. Consequently, these results suggest that continued stimulation through CD16 has the potential to impair natural cytotoxicity via attenuation of NKp46-dependent signals.

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Section: Discussionsupporting

confidence: 75%

Anti-HIV Antibody–Dependent Activation of NK Cells Impairs NKp46 Expression

Parsons

Tang

Jegaskanda

et al. 2014

The Journal of Immunology

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“…Importantly, changes in the environment in various disease settings result in the recruitment of specific NK cell subsets, allowing for greater disease control among certain patients (30,(35)(36)(37)(38). In AHCT for neuroblastoma, the presence of a "missing ligand" for inhibitory KIR was associated with improved survival, suggesting that normally hyporesponsive unlicensed NK cells are specifically recruited to control disease in this setting (39).…”

mentioning

confidence: 99%

KIR and HLA Genotypes Predictive of Low-Affinity Interactions Are Associated with Lower Relapse in Autologous Hematopoietic Cell Transplantation for Acute Myeloid Leukemia

Marra

Greene

Hwang

et al. 2015

The Journal of Immunology

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Killer cell Ig–like receptors (KIRs) bind cognate HLA class I ligands with distinct affinities, affecting NK cell licensing and inhibition. We hypothesized that differences in KIR and HLA class I genotypes predictive of varying degrees of receptor–ligand binding affinities influence clinical outcomes in autologous hematopoietic cell transplantation (AHCT) for acute myeloid leukemia (AML). Using genomic DNA from a homogeneous cohort of 125 AML patients treated with AHCT, we performed KIR and HLA class I genotyping and found that patients with a compound KIR3DL1+ and HLA-Bw4-80Thr+, HLA-Bw4-80Ile– genotype, predictive of low-affinity interactions, had a low incidence of relapse, compared with patients with a KIR3DL1+ and HLA-Bw4-80Ile+ genotype, predictive of high-affinity interactions (hazard ratio [HR], 0.22; 95% confidence interval [CI], 0.06–0.78; p = 0.02). This effect was influenced by HLA-Bw4 copy number, such that relapse progressively increased with one copy of HLA-Bw4-80Ile (HR, 1.6; 95% CI, 0.84–3.1; p = 0.15) to two to three copies (HR, 3.0; 95% CI, 1.4–6.5; p = 0.005) and progressively decreased with one to two copies of HLA-Bw4-80Thr (p = 0.13). Among KIR3DL1+ and HLA-Bw4-80Ile+ patients, a predicted low-affinity KIR2DL2/3+ and HLA-C1/C1 genotype was associated with lower relapse than a predicted high-affinity KIR2DL1+ and HLA-C2/C2 genotype (HR, 0.25; 95% CI, 0.09–0.73; p = 0.01). Similarly, a KIR3DL1+ and HLA-Bw4-80Thr+, HLA-Bw4-80Ile– genotype, or lack of KIR3DL1+ and HLA-Bw4-80Ile+ genotype, rescued KIR2DL1+ and HLA-C2/C2 patients from high relapse (p = 0.007). These findings support a role for NK cell graft-versus-leukemia activity modulated by NK cell receptor–ligand affinities in AHCT for AML.

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“…The functional potential of 46 SP stimulated with HLA-devoid K562 cells was assessed as previously described [4]. Briefly, cryopreserved PBMC were thawed and resuspended at 10 6 cells/ml in RPMI 1640 that contained 10% FBS, 2mM L-glutamine, 50 IU penicillin and 50µg/ml streptomycin (cRPMI) (all from Wisent).…”

Section: Nk Cell Activationmentioning

confidence: 99%

“…All subjects were HLA typed as previously described (4). KIR3DS/L1 genotyping was performed by PCR with 2 sets of sequence-specific primers (PCR-SSP) as previously described [4].…”

Section: Mhc and Kir Genotypingmentioning

confidence: 99%

“…Furthermore, individuals who carry the *h/*y+B*57 genotype have higher percentages of NK cells able to express the degranulation marker CD107a and secrete both Interferon-γ (IFN-γ) and Tumor Necrosis Factor-α (TNF-α) in response to stimulation with the HLAdevoid K562 cell line when compared to NK cells from individuals who carry either KIR3DL1*h/*y or HLA-B*57 alone [4]. The fact that NK cells from individuals carrying *h/*y+B*57 demonstrate higher functionality when stimulated with HLA-devoid target cells may explain the slower HIV disease course and superior VL control observed in HIV-infected slow progressors (SP) [12].…”

Section: Introductionmentioning

confidence: 99%

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Inhibitory Killer Immunoglobulin-like receptors to self HLA-B and HLA-C ligands contribute differentially to Natural Killer cell functional potential in HIV infected slow progressors

Kamya

Tallon

Melendez-Peña

et al. 2012

Clinical Immunology

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HIV Protective KIR3DL1 and HLA-B Genotypes Influence NK Cell Function Following Stimulation with HLA-Devoid Cells

Abstract: Material Supplementary 1.DC1http://www.jimmunol.org/content/suppl/2010/01/08/jimmunol.090262

Cited by 90 publications

References 57 publications

Anti-HIV Antibody–Dependent Activation of NK Cells Impairs NKp46 Expression

Anti-HIV Antibody–Dependent Activation of NK Cells Impairs NKp46 Expression

KIR and HLA Genotypes Predictive of Low-Affinity Interactions Are Associated with Lower Relapse in Autologous Hematopoietic Cell Transplantation for Acute Myeloid Leukemia

Inhibitory Killer Immunoglobulin-like receptors to self HLA-B and HLA-C ligands contribute differentially to Natural Killer cell functional potential in HIV infected slow progressors

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