Journal article

Heterozygosity for the common perforin mutation, p.A91V, impairs the cytotoxicity of primary natural killer cells from healthy individuals

Imran G House, Kevin Thia, Amelia J Brennan, Richard Tothill, Alexander Dobrovic, Wei Z Yeh, Richard Saffery, Zac Chatterton, Joseph A Trapani, Ilia Voskoboinik



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 ..

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Funding Acknowledgements

The work has been supported by Project and Program Grants from the National Health and Medical Research Council of Australia and the Cancer Council Victoria for IV and JAT; IV and RS are supported NH&MRC Fellowships; IGH is supported by an Australian Postgraduate Award. We wish to thank Assoc. Prof. Daniel Andrews for helpful suggestions and Jesse Rudd Schmidt for his contribution.