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KIRANDIS SIGNED

NK receptors and disease

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EC-Contrib. €

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Project "KIRANDIS" data sheet

The following table provides information about the project.

Coordinator
THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE 

Organization address
address: TRINITY LANE THE OLD SCHOOLS
city: CAMBRIDGE
postcode: CB2 1TN
website: www.cam.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Project website https://www.path.cam.ac.uk/directory/john-trowsdale
 Total cost 1˙735˙205 €
 EC max contribution 1˙735˙205 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-AdG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-10-01   to  2020-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE UK (CAMBRIDGE) coordinator 1˙735˙205.00

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 Project objective

NK cells are relevant to many kinds of disease, including viral infection, autoimmunity, cancer, transplantation and reproduction. The behavior of NK cells is controlled by a large number of different cell surface receptors, in a region on chromosome 19 called the LRC. Some of these receptors, such as KIR, are highly variable in gene number and allele sequence in different individuals. Many of them interact with HLA class I molecules, which are also highly polymorphic. To understand and exploit NK receptors and disease this project has three aims:

1. To investigate how variation in receptors encoded in the LRC influences viral infection and disease course. My laboratory is known for high-throughput KIR copy number and allele typing. Highly polymorphic KIR receptors are refractory to analysis by SNP typing and next generation sequencing (NGS) methods, so interrogation of large numbers of samples for accurate disease determination is not feasible. To overcome this problem we propose to develop digital PCR, sequence-based allele typing, imputation and NGS after sequence capture. Once underway, a large number of disease cohorts and matched controls will be investigated, spanning autoimmunity, infection and birth-weight, in collaboration with other laboratories.

2. To investigate mechanisms viruses use to evade NK cells. To facilitate this we have generated reporter cells that permit weak interaction of receptors with their ligands to be detected by production of Green Fluorescent Protein (GFP). The evasion of NK cells by HCMV, vaccinia and HPV viruses will be studied. This work will be in conjunction with expert virology groups in the UK.

3. To identify novel ligands for LRC-encoded receptors. We will use the reporter cells to screen for ligands, initially by blocking binding with monoclonal antibodies. We intend to identify ligands for KIR and LILR, where these are unknown, especially focusing on activating receptors.

 Publications

year authors and title journal last update
List of publications.
2019 Jyothi Jayaraman, Vitalina Kirgizova, Da Di, Christopher Johnson, Wei Jiang, James A. Traherne
qKAT: Quantitative Semi-automated Typing of Killer-cell Immunoglobulin-like Receptor Genes
published pages: , ISSN: 1940-087X, DOI: 10.3791/58646
Journal of Visualized Experiments 145 2020-01-23
2018 Lies Boelen, Bisrat Debebe, Marcos Silveira, Arafa Salam, Julia Makinde, Chrissy h. Roberts, Eddie C. Y. Wang, John Frater, Jill Gilmour, Katie Twigger, Kristin Ladell, Kelly L. Miners, Jyothi Jayaraman, James A. Traherne, David A. Price, Ying Qi, Maureen P. Martin, Derek C. Macallan, Chloe L. Thio, Jacquie Astemborski, Gregory Kirk, Sharyne M. Donfield, Susan Buchbinder, Salim I. Khakoo, James J.
Inhibitory killer cell immunoglobulin-like receptors strengthen CD8 + T cell–mediated control of HIV-1, HCV, and HTLV-1
published pages: eaao2892, ISSN: 2470-9468, DOI: 10.1126/sciimmunol.aao2892
Science Immunology 3/29 2020-01-23
2017 Ceri A Fielding, Michael P Weekes, Luis V Nobre, Eva Ruckova, Gavin S Wilkie, Joao A Paulo, Chiwen Chang, Nicolás M Suárez, James A Davies, Robin Antrobus, Richard J Stanton, Rebecca J Aicheler, Hester Nichols, Borek Vojtesek, John Trowsdale, Andrew J Davison, Steven P Gygi, Peter Tomasec, Paul J Lehner, Gavin W G Wilkinson
Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.22206
eLife 6 2020-01-23
2017 Adrian Kelly, John Trowsdale
Introduction: MHC/KIR and governance of specificity
published pages: 481-488, ISSN: 0093-7711, DOI: 10.1007/s00251-017-0986-6
Immunogenetics 69/8-9 2020-01-23
2017 Kattria van der Ploeg, Chiwen Chang, Martin A. Ivarsson, Ashley Moffett, Mark R. Wills, John Trowsdale
Modulation of Human Leukocyte Antigen-C by Human Cytomegalovirus Stimulates KIR2DS1 Recognition by Natural Killer Cells
published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2017.00298
Frontiers in Immunology 8 2020-01-23
2018 Suwit Chaisri, James A. Traherne, Jyothi Jayaraman, Amornrat Romphruk, John Trowsdale, Chanvit Leelayuwat
Novel KIR genotypes and gene copy number variations in northeastern Thais
published pages: 380-386, ISSN: 0019-2805, DOI: 10.1111/imm.12847
Immunology 153/3 2020-01-23
2017 Francesco Colucci, James Traherne
Killer-cell immunoglobulin-like receptors on the cusp of modern immunogenetics
published pages: 556-561, ISSN: 0019-2805, DOI: 10.1111/imm.12802
Immunology 152/4 2020-01-23
2017 James C Lee, Daniele Biasci, Rebecca Roberts, Richard B Gearry, John C Mansfield, Tariq Ahmad, Natalie J Prescott, Jack Satsangi, David C Wilson, Luke Jostins, Carl A Anderson, James A Traherne, Paul A Lyons, Miles Parkes, Kenneth G C Smith
Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn\'s disease
published pages: 262-268, ISSN: 1061-4036, DOI: 10.1038/ng.3755
Nature Genetics 49/2 2020-01-23
2018 Oisín Huhn, Olympe Chazara, Martin A. Ivarsson, Christelle Retière, Timothy C. Venkatesan, Paul J. Norman, Hugo G. Hilton, Jyothi Jayaraman, James A. Traherne, John Trowsdale, Mitsutero Ito, Christiane Kling, Peter Parham, Hormas Ghadially, Ashley Moffett, Andrew M. Sharkey, Francesco Colucci
High-Resolution Genetic and Phenotypic Analysis of KIR2DL1 Alleles and Their Association with Pre-Eclampsia
published pages: 2593-2601, ISSN: 0022-1767, DOI: 10.4049/jimmunol.1800860
The Journal of Immunology 201/9 2020-01-23
2017 Vivien Béziat, Hugo G. Hilton, Paul J. Norman, James A. Traherne
Deciphering the killer-cell immunoglobulin-like receptor system at super-resolution for natural killer and T-cell biology
published pages: 248-264, ISSN: 0019-2805, DOI: 10.1111/imm.12684
Immunology 150/3 2020-01-23
2018 Matthew D. Blunt, Pauline Rettman, Leidy Y. Bastidas-Legarda, Rebecca Fulton, Valentina Capizzuto, Mohammed M. Naiyer, James A. Traherne, Salim I. Khakoo
A novel antibody combination to identify KIR2DS2 high NK cells in KIR2DL3/L2/S2 heterozygous donors
published pages: , ISSN: 2059-2302, DOI: 10.1111/tan.13413
HLA 2020-01-23
2018 Maneesh K. Misra, Danillo G. Augusto, Gonzalo Montero Martin, Neda Nemat-Gorgani, Jürgen Sauter, Jan A. Hofmann, James A. Traherne, Betsy González-Quezada, Clara Gorodezky, Will P. Bultitude, Wesley Marin, Cynthia Vierra-Green, Kirsten M. Anderson, Antonio Balas, Jose L. Caro-Oleas, Elisa Cisneros, Francesco Colucci, Ravi Dandekar, Sally M. Elfishawi, Marcelo A. Fernández-Viña, Merhan Fouda, Rafael González-Fernández, Arend Große, Maria J. Herrero-Mata, Sam Q. Hollenbach, Steven G.E. Marsh, Alex Mentzer, Derek Middleton, Ashley Moffett, Miguel A. Moreno-Hidalgo, Ghada I. Mossallam, Annettee Nakimuli, Jorge R. Oksenberg, Stephen J. Oppenheimer, Peter Parham, Maria-Luiza Petzl-Erler, Dolores Planelles, Florentino Sánchez-García, Francisco Sánchez-Gordo, Alexander H. Schmidt, John Trowsdale, Luciana B. Vargas, Jose L. Vicario, Carlos Vilches, Paul J. Norman, Jill A. Hollenbach
Report from the Killer-cell Immunoglobulin-like Receptors (KIR) component of the 17th International HLA and Immunogenetics Workshop
published pages: , ISSN: 0198-8859, DOI: 10.1016/j.humimm.2018.10.003
Human Immunology 2020-01-23

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