title: Differential RNA expression of KIR alleles.
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.
authors.affiliation: Northern Ireland Regional Histocompatibility and Immunogenetics Laboratory, City Hospital, Belfast, Northern Ireland, UK.
authors.forename: Colum
authors.initials: C
authors.lastname: McErlean
authors.forename: Asensio A
authors.initials: AA
authors.lastname: Gonzalez
authors.forename: Rodat
authors.initials: R
authors.lastname: Cunningham
authors.forename: Ashley
authors.initials: A
authors.lastname: Meenagh
authors.forename: Tanya
authors.initials: T
authors.lastname: Shovlin
authors.forename: Derek
authors.initials: D
authors.lastname: Middleton
mesh_terms: D000483:Alleles; D018628:Gene Dosage; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics*; D054342:Receptors, KIR2DL1 / Q000235:genetics*; D054344:Receptors, KIR2DL3 / Q000235:genetics*; D054341:Receptors, KIR3DL1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C093100:KIR2DL1 protein, human; C515078:KIR2DL3 protein, human; C515083:KIR3DL1 protein, human; D012333:RNA, Messenger; D054342:Receptors, KIR2DL1; D054344:Receptors, KIR2DL3; D054341:Receptors, KIR3DL1
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