KIR Gene Mismatching and KIR/C Ligands in Liver Transplantation

Legáz, Isabel; López-Álvarez, María R.; Campillo, José A.; Moya‐Quiles, María Rosa; Bolarín, José Miguel; Peña, J. de la; Salgado, Gema; Gimeno, Lourdes; García‐Alonso, Ana M.; Muro, Manuel; Miras, M.; Alonso, Clara; Álvarez-López, María R.; Minguela, Alfredo

doi:10.1097/tp.0b013e318286486c

Cited by 36 publications

(58 citation statements)

References 67 publications

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“…HLA-C and KIR typing was performed as previously described. 21 HLA-C genotyping allowed distinction between HLA-C Asn80 (group-C1) and HLA-C…”

Section: Hla-a -B and -C And Kir Genotypingmentioning

confidence: 99%

“…Therefore, not only the diverse receptors expressed on the NK cell, but also the inhibitory and activating ligands expressed on the target cells will determine NK cell response, susceptibility to autoimmunity, 17 infection, 18 and cancer, 19 and the outcome of allogeneic stem cell transplantation (SCT), 20 or liver transplantation. 21 Malignant cells usually over-express ligands for activating receptors, 16,22 and reduce the expression of inhibitory ones (HLA-I). 23,24 With respect to this, it has been described that myeloma cells express ligands for NK cell activating receptors, 25,26 but only scarce and contradictory results concerning the expression of inhibitory ligands (HLA-I).…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of KIR inhibitory ligands (HLA-I) determines that immunosurveillance of myeloma depends on diverse and strong NK cell licensing

Martínez‐Sánchez¹,

Periago

Legáz³

et al. 2016

OncoImmunology

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L3¡ (20% vs. 83%, p < 0.00001) as well as KIR3DL1 ¡ (23% vs. 82%, p < 0.00001) genotypes had a dramatic negative impact on the 3-y progression-free survival (PFS), particularly in patients with lowtumor burden. Remarkably, myeloma-PCs, compared to K562 and other hematological cancers, showed substantial over-expression of HLA-I ("increasing-self" instead of missing-self), including HLA-C, and mild expression of ligands for NKc activating receptors (aRec) CD112, CD155, ULBP-1 and MICA/B, which apparently renders myeloma-PCs susceptible to lysis mainly by licensed NKc. KIR2DL1patients (with no conventional iKIR2D/HLA-C licensing interactions) lyse K562 but barely lyse myelomaPCs (4% vs. 15%; p < 0.05, compared to controls). These results support a model where immunosurveillance of no-missing-self cancers, e.g., myeloma, mainly depends on NKc licensing.

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“…HLA-C and KIR typing was performed as previously described. 21 HLA-C genotyping allowed distinction between HLA-C Asn80 (group-C1) and HLA-C…”

Section: Hla-a -B and -C And Kir Genotypingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Overexpression of KIR inhibitory ligands (HLA-I) determines that immunosurveillance of myeloma depends on diverse and strong NK cell licensing

Martínez‐Sánchez¹,

Periago

Legáz³

et al. 2016

OncoImmunology

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“…The HLA-C1 ligand carries an asparagine at position 80 (HLA-Cw01, 03, 07, 08, 09, 10, 12, 14) and HLA-C2 has a lysine at position 80 (HLA-Cw02, 04, 05, 06, 15) [7]. Within iKIRs, KIR2DL1 recognizes HLA-C2 ligand, whereas KIR2DL2/3 recognizes HLA-C1 ligand [8]. In aKIRs, binding to HLA-C has only been demonstrated for KIR2DS1 and KIR2DS4.…”

Section: Introductionmentioning

confidence: 99%

“…In aKIRs, binding to HLA-C has only been demonstrated for KIR2DS1 and KIR2DS4. KIR2DS1 recognizes HLA-C2 ligand, whereas KIR2DS4 recognizes HLA-C2 and a limited number of HLA-C1 ligands; ligands for other aKIRs remain elusive [8]. …”

Section: Introductionmentioning

confidence: 99%

“…Previous studies utilized several KIR models such as KIR gene-gene mismatch, HLA-C genotype mismatch, and KIR-ligand mismatch for donors lacking ligands for inhibitory KIR, which present in recipients [589]. In liver transplantation (LT), previous studies reported the impact of HLA-C allotypes on acute rejection (AR) and graft survival [910111213], but some studies demonstrated no effect on graft outcomes [14].…”

Section: Introductionmentioning

confidence: 99%

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Human Leukocyte Antigen-C Genotype and Killer Immunoglobulin-like Receptor-Ligand Matching in Korean Living Donor Liver Transplantation

Lee

Park

et al. 2017

Ann Lab Med

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BackgroundThe interaction between killer immunoglobulin-like receptors (KIRs) and HLA class I regulates natural killer (NK) cell cytotoxicity and function. The impact of NK cell alloreactivity through KIR in liver transplantation remains unelucidated. Since the frequency of HLA-C and KIR genotypes show ethnic differences, we assessed the impact of HLA-C, KIR genotype, or KIR-ligand mismatch on the allograft outcome of Korean liver allografts.MethodsOne hundred eighty-two living donor liver transplant patients were studied. Thirty-five patients (19.2%) had biopsy-confirmed acute rejection (AR), and eighteen (9.9%) had graft failure. The HLA-C compatibility, KIR genotypes, ligand-ligand, and KIR-ligand matching was retrospectively investigated for association with allograft outcomes.ResultsHomozygous C1 ligands were predominant in both patients and donors, and frequency of the HLA-C2 allele in Koreans was lower than that in other ethnic groups. Despite the significantly lower frequency of the HLA-C2 genotype in Koreans, donors with at least one HLA-C2 allele showed higher rates of AR than donors with no HLA-C2 alleles (29.2% vs 15.7%, P=0.0423). Although KIR genotypes also showed ethnic differences, KIR genotypes and the number of activating KIR/inhibitory KIR were not associated with the allograft outcome. KIR-ligand mismatch was expected in 31.6% of Korean liver transplants and had no impact on AR or graft survival.ConclusionsThis study could not confirm the clinical impact of KIR genotypes and KIR-ligand mismatch. However, we demonstrated that the presence of HLA-C2 allele in the donor influenced AR of Korean liver allografts.

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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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KIR Gene Mismatching and KIR/C Ligands in Liver Transplantation

Abstract: This study shows that KIR gene-gene MMs increase AR and that KIRs/C ligands associated to AR and KIR2DS4/C ligands also influence short-term graft survival.

Cited by 36 publications

References 67 publications

Overexpression of KIR inhibitory ligands (HLA-I) determines that immunosurveillance of myeloma depends on diverse and strong NK cell licensing

Overexpression of KIR inhibitory ligands (HLA-I) determines that immunosurveillance of myeloma depends on diverse and strong NK cell licensing

Human Leukocyte Antigen-C Genotype and Killer Immunoglobulin-like Receptor-Ligand Matching in Korean Living Donor Liver Transplantation

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

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