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Differential RNA expression of KIR alleles

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Abstract

Allelic polymorphisms dramatically influence the phenotype of human killer immunoglobulin-like receptors (KIR) by modifying their expression in cell surfaces. It is unclear though to what extent this involves transcriptional or post-transcriptional mechanisms, as quantitative RNA expression of KIR alleles has not been systematically compared. We measured RNA transcript abundance of common KIR alleles by real-time quantitative reverse transcriptase PCR (RT-PCR) in 85 PBL samples that were allele-typed in parallel. Allele type showed little influence on transcript abundance for a given KIR gene, except for: (1) KIR2DL5B*002, which consistently showed undetectable transcripts levels; (2) truncated KIR2DS4 alleles, associated with lowered expression levels; and (3) alleles of KIR2DL4 with a single-base deletion, associated with higher expression than average. Lowered levels of truncated KIR2DS4 transcripts were confirmed by dot blot of RT-PCR products, indicating imbalanced allelic RNA expression in heterozygote genotypes containing these alleles. Imbalanced expression of truncated KIR2DS4 alleles was corroborated in family samples. Gene copy number of KIR2DL1, KIR2DL3 and KIR3DL1 influenced RNA expression, genotypes with a single copy expressing on average lower transcript amounts than those with two copies. The data show that for a given KIR gene, the common allele types found in our population express comparable RNA levels, except truncated or null alleles. Thus, variation of KIR expression on cell surfaces more likely involves post-transcriptional mechanisms.

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Notes

  1. The 95% confidence interval of the C p value is defined by mean ± 2 SD, so that ∆C p = 4 SD. Assuming that amplicon amounts double every cycle, the corresponding amplicon amount range is \( {2^{\Delta {C_{\rm{p}}}}} \).

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Authors and Affiliations

  1. Northern Ireland Regional Histocompatibility and Immunogenetics Laboratory, City Hospital, Belfast, Northern Ireland, UK

    Colum McErlean, Asensio A. Gonzalez, Ashley Meenagh & Tanya Shovlin

  2. Institute of Agri-Food & Land Use, School of Biological Sciences, Queen’s University, Belfast, Northern Ireland, UK

    Rodat Cunningham

  3. Division of Immunology and School of Infection and Host Defence, Royal Liverpool University Hospital, Liverpool, UK

    Derek Middleton

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  1. Colum McErlean
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  2. Asensio A. Gonzalez
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  4. Ashley Meenagh
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  5. Tanya Shovlin
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  6. Derek Middleton
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Correspondence to Asensio A. Gonzalez.

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McErlean, C., Gonzalez, A.A., Cunningham, R. et al. Differential RNA expression of KIR alleles. Immunogenetics 62, 431–440 (2010). https://doi.org/10.1007/s00251-010-0449-9

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