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Article ; Online: KIR in Allogeneic Hematopoietic Stem Cell Transplantation: Need for a Unified Paradigm for Donor Selection.

Dhuyser, Adèle / Aarnink, Alice / Pérès, Michaël / Jayaraman, Jyothi / Nemat-Gorgani, Neda / Rubio, Marie Thérèse / Trowsdale, John / Traherne, James

Frontiers in immunology

2022 Volume 13, Page(s) 821533

Abstract: Allogeneic hematopoietic stem cell transplantation (aHSCT) is a lifesaving therapy for hematological malignancies. For years, a fully matched HLA donor was a requisite for the procedure. However, new immunosuppressive strategies have enabled the ... ...

Abstract	Allogeneic hematopoietic stem cell transplantation (aHSCT) is a lifesaving therapy for hematological malignancies. For years, a fully matched HLA donor was a requisite for the procedure. However, new immunosuppressive strategies have enabled the recruitment of viable alternative donors, particularly haploidentical donors. Over 95% of patients have at least two potential haploidentical donors available to them. To identify the best haploidentical donor, the assessment of new immunogenetic criteria could help. To this end, the clinical benefit of KIR genotyping in aHSCT has been widely studied but remains contentious. This review aims to evaluate the importance of KIR-driven NK cell alloreactivity in the context of aHSCT and explain potential reasons for the discrepancies in the literature. Here, through a non-systematic review, we highlight how the studies in this field and their respective predictive models or scoring strategies could be conceptually opposed, explaining why the role of NK cells remains unclear in aHCST outcomes. We evaluate the limitations of each published prediction model and describe how every scoring strategy to date only partly delivers the requirements for optimally effective NK cells in aHSCT. Finally, we propose approaches toward finding the optimal use of KIR genotyping in aHSCT for a unified criterion for donor selection.
MeSH term(s)	Donor Selection/methods ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Killer Cells, Natural ; Receptors, KIR/genetics ; Tissue Donors
Chemical Substances	Receptors, KIR
Language	English
Publishing date	2022-02-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.821533
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Article ; Online: KIR copy number variations in dengue-infected patients from northeastern Thailand.

Chaisri, Suwit / Jayaraman, Jyothi / Mongkolsapaya, Juthathip / Duangchinda, Thaniya / Jumniansong, Amonrat / Trowsdale, John / Traherne, James A / Leelayuwat, Chanvit

Human immunology

2022 Volume 83, Issue 4, Page(s) 328–334

Abstract: Killer immunoglobulin-like receptors (KIRs) are a family of receptors expressed on Natural killer (NK) cells. The extensive polymorphism of KIR is involved in the immune responses of NK cells and influences dengue infections. We investigated the ... ...

Abstract	Killer immunoglobulin-like receptors (KIRs) are a family of receptors expressed on Natural killer (NK) cells. The extensive polymorphism of KIR is involved in the immune responses of NK cells and influences dengue infections. We investigated the diversity of KIR copy numbers in dengue-infected patients from northeastern Thailand. Copy numbers of KIRs were determined by quantitative polymerase chain reaction in 137 dengue-infected patients, comprising 63 dengue fever (DF) and 74 dengue hemorrhagic fever (DHF). The distribution of KIRs was observed to be between 0 and 4 copies. The KIR AA genotype with heterozygous KIR2DS4D/WT was the most common in dengue patients, 25.4% DF and 23% DHF. Forty KIR profiles were determined in dengue patients, including 31 usual, 6 expanded, and 3 contracted profiles. Investigation of KIR copy number and dengue severity indicated that two copies of KIR2DL3 combined with HLA-C1C1 associated with an increased risk of DHF (OR 2.32, 95% CI 1.159-4.624, P = 0.016), whereas one copy of KIR2DL2 and KIR2DL3 together with HLA-C1C1 associated with a reduced risk of DHF (OR 0.17, 95% CI 0.058-0.482, P < 0.001). The outcomes of this study will contribute to the understanding of KIR complexity and innate immune responses in dengue infections.
MeSH term(s)	DNA Copy Number Variations ; Dengue/genetics ; Genotype ; HLA Antigens/genetics ; Humans ; Receptors, KIR/genetics ; Thailand
Chemical Substances	HLA Antigens ; Receptors, KIR
Language	English
Publishing date	2022-01-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	801524-7
ISSN	1879-1166 ; 0198-8859
ISSN (online)	1879-1166
ISSN	0198-8859
DOI	10.1016/j.humimm.2022.01.005
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Zs.A 1597: Show issues

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Article ; Online: Human MHC architecture and evolution: implications for disease association studies.

Traherne, J A

International journal of immunogenetics

2008 Volume 35, Issue 3, Page(s) 179–192

Abstract: Major histocompatibility complex (MHC) variation is a key determinant of susceptibility and resistance to a large number of infectious, autoimmune and other diseases. Identification of the MHC variants conferring susceptibility to disease is problematic, ...

Abstract	Major histocompatibility complex (MHC) variation is a key determinant of susceptibility and resistance to a large number of infectious, autoimmune and other diseases. Identification of the MHC variants conferring susceptibility to disease is problematic, due to high levels of variation and linkage disequilibrium. Recent cataloguing and analysis of variation over the complete MHC has facilitated localization of susceptibility loci for autoimmune diseases, and provided insight into the MHC's evolution. This review considers how the unusual genetic characteristics of the MHC impact on strategies to identify variants causing, or contributing to, disease phenotypes. It also considers the MHC in relation to novel mechanisms influencing gene function and regulation, such as epistasis, epigenetics and microRNAs. These developments, along with recent technological advances, shed light on genetic association in complex disease.
MeSH term(s)	Alleles ; Biological Evolution ; Epigenesis, Genetic ; Epistasis, Genetic ; Genetic Linkage ; Genetic Predisposition to Disease ; Genetic Variation ; Genotype ; Haplotypes ; Humans ; Major Histocompatibility Complex/genetics ; Major Histocompatibility Complex/immunology ; MicroRNAs/genetics ; Multigene Family ; Phenotype ; Polymorphism, Genetic
Chemical Substances	MicroRNAs
Language	English
Publishing date	2008-04-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2177883-8
ISSN	1744-313X ; 1744-3121
ISSN (online)	1744-313X
ISSN	1744-3121
DOI	10.1111/j.1744-313X.2008.00765.x
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Zs.A 994: Show issues

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Article ; Online: Comparison of NK alloreactivity prediction models based on KIR-MHC interactions in haematopoietic stem cell transplantation.

Dhuyser, Adèle / Remen, Thomas / Pérès, Michaël / Chamberlain-Evans, Vitalina / Nemat-Gorgani, Neda / Campidelli, Arnaud / Clément, Sandra / Rubio, Marie Thérèse / Trowsdale, John / Aarnink, Alice / Traherne, James

Frontiers in immunology

2023 Volume 14, Page(s) 1028162

Abstract: The biological processes underlying NK cell alloreactivity in haematopoietic stem cell transplantation (HSCT) remain unclear. Many different models to predict NK alloreactivity through KIR and MHC genotyping exist, raising ambiguities in its utility and ... ...

Abstract	The biological processes underlying NK cell alloreactivity in haematopoietic stem cell transplantation (HSCT) remain unclear. Many different models to predict NK alloreactivity through KIR and MHC genotyping exist, raising ambiguities in its utility and application for clinicians. We assessed 27 predictive models, broadly divided into six categories of alloreactivity prediction: ligand-ligand, receptor-ligand, educational, KIR haplotype-based, KIR matching and KIR allelic polymorphism. The models were applied to 78 NGS-typed donor/recipient pairs undergoing allogeneic HSCT in genoidentical (n=43) or haploidentical (n=35) matchings. Correlations between different predictive models differed widely, suggesting that the choice of the model in predicting NK alloreactivity matters. For example, two broadly used models,
MeSH term(s)	Humans ; Ligands ; Receptors, KIR/genetics ; Hematopoietic Stem Cell Transplantation/adverse effects ; Killer Cells, Natural ; Graft vs Host Disease/etiology
Chemical Substances	Ligands ; Receptors, KIR
Language	English
Publishing date	2023-03-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1028162
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Article ; Online: Deciphering the killer-cell immunoglobulin-like receptor system at super-resolution for natural killer and T-cell biology.

Béziat, Vivien / Hilton, Hugo G / Norman, Paul J / Traherne, James A

Immunology

2017 Volume 150, Issue 3, Page(s) 248–264

Abstract: Killer-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 ... ...

Abstract	Killer-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.
MeSH term(s)	Adaptive Immunity ; Animals ; Biological Evolution ; Female ; Genotype ; Humans ; Immunity, Innate ; Killer Cells, Natural/immunology ; Placentation/immunology ; Polymorphism, Genetic ; Pregnancy ; Receptors, KIR/genetics ; Receptors, KIR/metabolism ; T-Lymphocytes/immunology
Chemical Substances	Receptors, KIR
Language	English
Publishing date	2017-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80124-0
ISSN	1365-2567 ; 0019-2805 ; 0953-4954
ISSN (online)	1365-2567
ISSN	0019-2805 ; 0953-4954
DOI	10.1111/imm.12684
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Ud II Zs.181: Show issues

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Article ; Online: qKAT: Quantitative Semi-automated Typing of Killer-cell Immunoglobulin-like Receptor Genes.

Jayaraman, Jyothi / Kirgizova, Vitalina / Di, Da / Johnson, Christopher / Jiang, Wei / Traherne, James A

Journal of visualized experiments : JoVE

2019 , Issue 145

Abstract: Killer cell immunoglobulin-like receptors (KIRs) are a set of inhibitory and activating immune receptors, on natural killer (NK) and T cells, encoded by a polymorphic cluster of genes on chromosome 19. Their best-characterized ligands are the human ... ...

Abstract	Killer cell immunoglobulin-like receptors (KIRs) are a set of inhibitory and activating immune receptors, on natural killer (NK) and T cells, encoded by a polymorphic cluster of genes on chromosome 19. Their best-characterized ligands are the human leukocyte antigen (HLA) molecules that are encoded within the major histocompatibility complex (MHC) locus on chromosome 6. There is substantial evidence that they play a significant role in immunity, reproduction, and transplantation, making it crucial to have techniques that can accurately genotype them. However, high-sequence homology, as well as allelic and copy number variation, make it difficult to design methods that can accurately and efficiently genotype all KIR genes. Traditional methods are usually limited in the resolution of data obtained, throughput, cost-effectiveness, and the time taken for setting up and running the experiments. We describe a method called quantitative KIR semi-automated typing (qKAT), which is a high-throughput multiplex real-time polymerase chain reaction method that can determine the gene copy numbers for all genes in the KIR locus. qKAT is a simple high-throughput method that can provide high-resolution KIR copy number data, which can be further used to infer the variations in the structurally polymorphic haplotypes that encompass them. This copy number and haplotype data can be beneficial for studies on large-scale disease associations, population genetics, as well as investigations on expression and functional interactions between KIR and HLA.
MeSH term(s)	Automation ; DNA Copy Number Variations/genetics ; Haplotypes ; Humans ; Linkage Disequilibrium/genetics ; Receptors, KIR/genetics ; Software
Chemical Substances	Receptors, KIR
Language	English
Publishing date	2019-03-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/58646
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Article ; Online: KIR-HLA interactions extend human CD8+ T cell lifespan in vivo.

Zhang, Yan / Yan, Ada Wc / Boelen, Lies / Hadcocks, Linda / Salam, Arafa / Gispert, Daniel Padrosa / Spanos, Loiza / Bitria, Laura Mora / Nemat-Gorgani, Neda / Traherne, James A / Roberts, Chrissy / Koftori, Danai / Taylor, Graham P / Forton, Daniel / Norman, Paul J / Marsh, Steven Ge / Busch, Robert / Macallan, Derek C / Asquith, Becca

The Journal of clinical investigation

2023 Volume 133, Issue 12

Abstract: BACKGROUNDThere is increasing evidence, in transgenic mice and in vitro, that inhibitory killer cell immunoglobulin-like receptors (iKIRs) can modulate T cell responses. Furthermore, we have previously shown that iKIRs are an important determinant of T ... ...

Abstract	BACKGROUNDThere is increasing evidence, in transgenic mice and in vitro, that inhibitory killer cell immunoglobulin-like receptors (iKIRs) can modulate T cell responses. Furthermore, we have previously shown that iKIRs are an important determinant of T cell-mediated control of chronic viral infection and that these results are consistent with an increase in the CD8+ T cell lifespan due to iKIR-ligand interactions. Here, we tested this prediction and investigated whether iKIRs affect T cell lifespan in humans in vivo.METHODSWe used stable isotope labeling with deuterated water to quantify memory CD8+ T cell survival in healthy individuals and patients with chronic viral infections.RESULTSWe showed that an individual's iKIR-ligand genotype was a significant determinant of CD8+ T cell lifespan: in individuals with 2 iKIR-ligand gene pairs, memory CD8+ T cells survived, on average, for 125 days; in individuals with 4 iKIR-ligand gene pairs, the memory CD8+ T cell lifespan doubled to 250 days. Additionally, we showed that this survival advantage was independent of iKIR expression by the T cell of interest and, further, that the iKIR-ligand genotype altered the CD8+ and CD4+ T cell immune aging phenotype.CONCLUSIONSTogether, these data reveal an unexpectedly large effect of iKIR genotype on T cell survival.FUNDINGWellcome Trust; Medical Research Council; EU Horizon 2020; EU FP7; Leukemia and Lymphoma Research; National Institute of Health Research (NIHR) Imperial Biomedical Research Centre; Imperial College Research Fellowship; National Institutes of Health; Jefferiss Trust.
MeSH term(s)	United States ; Mice ; Animals ; Humans ; Longevity ; Ligands ; Killer Cells, Natural ; Receptors, KIR/genetics ; Receptors, KIR/metabolism ; CD8-Positive T-Lymphocytes/metabolism
Chemical Substances	Ligands ; Receptors, KIR
Language	English
Publishing date	2023-06-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI169496
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Article ; Online: Novel KIR genotypes and gene copy number variations in northeastern Thais.

Chaisri, Suwit / Traherne, James A / Jayaraman, Jyothi / Romphruk, Amornrat / Trowsdale, John / Leelayuwat, Chanvit

Immunology

2017 Volume 153, Issue 3, Page(s) 380–386

Abstract: KIR (Killer Immunoglobulin-like Receptor) variants influence immune responses and are genetic factors in disease susceptibility. Using sequence-specific priming PCR, we have previously described the diversity of KIR genes in term of presence/absence in ... ...

Abstract	KIR (Killer Immunoglobulin-like Receptor) variants influence immune responses and are genetic factors in disease susceptibility. Using sequence-specific priming PCR, we have previously described the diversity of KIR genes in term of presence/absence in northeastern Thais (NETs). To provide additional resolution beyond conventional methods, quantitative PCR was applied to determine KIR copy number profiles. Novel expanded and contracted KIR copy number profiles were identified at cumulatively high frequencies. These all comprise haplotypes with duplication (6·9%) or deletion (2·7%) of KIR3DL1/S1 along with adjacent genes. Five expanded KIR profiles comprised haplotypes with duplications of KIR2DP1, 2DL1, 3DP1, 2DL4, 3DL1/S1 and 2DS1/4, whereas two contracted profiles contained only a single copy of KIR3DP1, 3DL1/S1 and 2DL4. Using a KIR haplotype prediction program (KIR Haplotype Identifier), 14% of NET haplotypes carried atypical haplotypes based on the gene copy number data.
MeSH term(s)	DNA Copy Number Variations/genetics ; Haplotypes/genetics ; Humans ; Receptors, KIR/genetics ; Thailand
Chemical Substances	Receptors, KIR
Language	English
Publishing date	2017-10-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80124-0
ISSN	1365-2567 ; 0019-2805 ; 0953-4954
ISSN (online)	1365-2567
ISSN	0019-2805 ; 0953-4954
DOI	10.1111/imm.12847
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Ud II Zs.181: Show issues

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Article ; Online: The CD94/NKG2A inhibitory receptor educates uterine NK cells to optimize pregnancy outcomes in humans and mice.

Shreeve, Norman / Depierreux, Delphine / Hawkes, Delia / Traherne, James A / Sovio, Ulla / Huhn, Oisin / Jayaraman, Jyothi / Horowitz, Amir / Ghadially, Hormas / Perry, John R B / Moffett, Ashley / Sled, John G / Sharkey, Andrew M / Colucci, Francesco

Immunity

2021 Volume 54, Issue 6, Page(s) 1231–1244.e4

Abstract: The conserved CD94/NKG2A inhibitory receptor is expressed by nearly all human and ∼50% of mouse uterine natural killer (uNK) cells. Binding human HLA-E and mouse Qa-1, NKG2A drives NK cell education, a process of unknown physiological importance ... ...

Abstract	The conserved CD94/NKG2A inhibitory receptor is expressed by nearly all human and ∼50% of mouse uterine natural killer (uNK) cells. Binding human HLA-E and mouse Qa-1, NKG2A drives NK cell education, a process of unknown physiological importance influenced by HLA-B alleles. Here, we show that NKG2A genetic ablation in dams mated with wild-type males caused suboptimal maternal vascular responses in pregnancy, accompanied by perturbed placental gene expression, reduced fetal weight, greater rates of smaller fetuses with asymmetric growth, and abnormal brain development. These are features of the human syndrome pre-eclampsia. In a genome-wide association study of 7,219 pre-eclampsia cases, we found a 7% greater relative risk associated with the maternal HLA-B allele that does not favor NKG2A education. These results show that the maternal HLA-B→HLA-E→NKG2A pathway contributes to healthy pregnancy and may have repercussions on offspring health, thus establishing the physiological relevance for NK cell education. VIDEO ABSTRACT.
MeSH term(s)	Animals ; Female ; Genome-Wide Association Study/methods ; HLA Antigens/immunology ; Humans ; Killer Cells, Natural/immunology ; Male ; Mice ; Mice, Inbred C57BL ; NK Cell Lectin-Like Receptor Subfamily C/immunology ; NK Cell Lectin-Like Receptor Subfamily D/immunology ; Placenta/immunology ; Pregnancy ; Pregnancy Outcome ; Uterus/immunology
Chemical Substances	HLA Antigens ; KLRC1 protein, human ; KLRD1 protein, human ; NK Cell Lectin-Like Receptor Subfamily C ; NK Cell Lectin-Like Receptor Subfamily D
Language	English
Publishing date	2021-04-21
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2021.03.021
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Zs.A 4227: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 69: Show issues

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Article ; Online: Surveillance of cell and tissue perturbation by receptors in the LRC.

Trowsdale, John / Jones, Des C / Barrow, Alexander D / Traherne, James A

Immunological reviews

2015 Volume 267, Issue 1, Page(s) 117–136

Abstract: The human leukocyte receptor complex (LRC) encompasses several sets of genes with a common evolutionary origin and which form a branch of the immunoglobulin superfamily (IgSF). Comparisons of LRC genes both within and between species calls for a high ... ...

Abstract	The human leukocyte receptor complex (LRC) encompasses several sets of genes with a common evolutionary origin and which form a branch of the immunoglobulin superfamily (IgSF). Comparisons of LRC genes both within and between species calls for a high degree of plasticity. The drive for this unprecedented level of variation is not known, but it relates in part to interaction of several LRC products with polymorphic human leukocyte antigen (HLA) class I molecules. However, the range of other proposed ligands for LRC products indicates a dynamic set of receptors that have adapted to detect target molecules relating to numerous cellular pathways. Several receptors in the complex bind a molecular signature in collagenous ligands. Others detect a variety of motifs relating to pathogens in addition to cellular stress, attesting to the opportunistic versatility of LRC receptors.
MeSH term(s)	Genetic Variation/genetics ; Genetic Variation/immunology ; HLA Antigens/genetics ; HLA Antigens/immunology ; Histocompatibility Antigens Class I/genetics ; Histocompatibility Antigens Class I/immunology ; Humans ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism ; Leukocytes/immunology ; Leukocytes/metabolism ; Ligands ; Models, Genetic ; Models, Immunological ; Receptors, Immunologic/genetics ; Receptors, Immunologic/immunology
Chemical Substances	HLA Antigens ; Histocompatibility Antigens Class I ; Ligands ; Receptors, Immunologic
Language	English
Publishing date	2015-07-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/imr.12314
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