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DC Field | Value | Language |
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dc.contributor.author | House, Imran G | en |
dc.contributor.author | Thia, Kevin | en |
dc.contributor.author | Brennan, Amelia J | en |
dc.contributor.author | Tothill, Richard | en |
dc.contributor.author | Dobrovic, Alexander | en |
dc.contributor.author | Yeh, Wei Z | en |
dc.contributor.author | Saffery, Richard | en |
dc.contributor.author | Chatterton, Zac | en |
dc.contributor.author | Trapani, Joseph A | en |
dc.contributor.author | Voskoboinik, Ilia | en |
dc.date.accessioned | 2015-05-16T02:24:52Z | |
dc.date.available | 2015-05-16T02:24:52Z | |
dc.date.issued | 2015-03-17 | en |
dc.identifier.citation | Immunology and Cell Biology 2015; 93(6): 575-80 | en |
dc.identifier.govdoc | 25776844 | en |
dc.identifier.other | PUBMED | en |
dc.identifier.uri | https://ahro.austin.org.au/austinjspui/handle/1/12686 | en |
dc.description.abstract | The production and delivery of functional perforin (PRF; PRF1 gene) by cytotoxic lymphocytes maintains immune homeostasis and tumour immune surveillance. In humans, inheritance of the common PRF1 polymorphism, p.A91V, (c.272C>T) found in 8-9% of the Caucasian population, with another mutated allele resulting in reduced PRF function or trafficking, has been shown to result in hyperinflammatory diseases and/or haematological cancers. In this study, we sought to investigate the function of p.A91V on a wild-type (WT) perforin background. We first developed an assay that distinguishes the relative levels of transcription of individual PRF1 alleles, including p.A91V. The p.A91V allele was seen to be expressed at similar levels as the WT allele in primary human natural killer (NK) cells, ruling out that allelic expression imbalance influenced their function. We then demonstrated that the p.A91V mutation results in protein misfolding and an appreciable reduction in NK-cell cytotoxicity in healthy carriers of p.A91V. We propose that this level of cytotoxic dysfunction may readily account for the predisposition to immune-mediated disease in individuals homozygous for p.A91V. Also, the fact that monoallelic mutations of PRF1 decrease NK-cell cytotoxicity should be considered in individuals presenting with the manifestations of immune deficiency states that impinge on NK-cell cytotoxicity.Immunology and Cell Biology advance online publication, 17 March 2015; doi:10.1038/icb.2015.1. | en |
dc.language.iso | en | en |
dc.title | Heterozygosity for the common perforin mutation, p.A91V, impairs the cytotoxicity of primary natural killer cells from healthy individuals. | en |
dc.type | Journal Article | en |
dc.identifier.journaltitle | Immunology and cell biology | en |
dc.identifier.affiliation | Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia | en |
dc.identifier.affiliation | Murdoch Children's Research Institute; Department of Paediatrics; The University of Melbourne; Royal Children's Hospital, Melbourne, Victoria, Australia | en |
dc.identifier.affiliation | Ludwig Institute for Cancer Research, Olivia Newton-John Cancer and Wellness Centre, Heidelberg (Melbourne), Victoria, Australia | en |
dc.identifier.affiliation | Department of Immunology and Microbiology, Parkville, Victoria, Australia | en |
dc.identifier.affiliation | Sir Peter MacCallum Department of Oncology, Parkville, Victoria, Australia | en |
dc.identifier.affiliation | Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia | en |
dc.identifier.affiliation | Department of Genetics, University of Melbourne, Parkville, Victoria, Australia | en |
dc.identifier.affiliation | Department of Pathology, University of Melbourne, Parkville, Victoria, Australia | en |
dc.identifier.doi | 10.1038/icb.2015.1 | en |
dc.relation.url | https://pubmed.ncbi.nlm.nih.gov/25776844 | en |
dc.type.austin | Journal Article | en |
local.name.researcher | Dobrovic, Alexander | |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.cerifentitytype | Publications | - |
item.fulltext | No Fulltext | - |
item.grantfulltext | none | - |
item.languageiso639-1 | en | - |
item.openairetype | Journal Article | - |
crisitem.author.dept | Olivia Newton-John Cancer Research Institute | - |
crisitem.author.dept | Surgery (University of Melbourne) | - |
Appears in Collections: | Journal articles |
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