Two Lineages of KLRA with Contrasting Transcription Patterns Have Been Conserved at a Single Locus during Ruminant Speciation.

Mark S Gibson,James Birch,Nicholas D Sanderson,John A Hammond,Simon Gubbins,Alasdair J Allan,Shirley A Ellis

doi:10.4049/jimmunol.1801363

Mark S Gibson, James Birch + Show 5 more

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https://doi.org/10.4049/jimmunol.1801363

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Cattle possess the most diverse repertoire of NK cell receptor genes among all mammals studied to date. Killer cell receptor genes encoded within the NK complex and killer cell Ig-like receptor genes encoded within the leukocyte receptor complex have both been expanded and diversified. Our previous studies identified two divergent and polymorphic KLRA alleles within the NK complex in the Holstein-Friesian breed of dairy cattle. By examining a much larger cohort and other ruminant species, we demonstrate the emergence and fixation of two KLRA allele lineages (KLRA*01 and -*02) at a single locus during ruminant speciation. Subsequent recombination events between these allele lineages have increased the frequency of KLRA*02 extracellular domains. KLRA*01 and KLRA*02 transcription levels contrasted in response to cytokine stimulation, whereas homozygous animals consistently transcribed higher levels of KLRA, regardless of the allele lineage. KLRA*02 mRNA levels were also generally higher than KLRA*01 Collectively, these data point toward alternative functional roles governed by KLRA genotype and allele lineage. On a background of high genetic diversity of NK cell receptor genes, this KLRA allele fixation points to fundamental and potentially differential function roles.

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We have previously shown that the killer cell Ig-like receptor (KIR) and KLRC/D are differentially transcribed between cattle NK cells and that this mRNA expression is influenced by the MHC genotype [20]
The two divergent allele lineages of cattle KLRA are the products of a single locus Cattle contain a unique and expanded NK cell receptor gene repertoire that creates diversity in the NK cell population
This study examines KLRA complexity in a large and diverse cohort of cattle to develop a greater understanding of its potential importance in cattle immune responses

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Introduction

KLRA*01 and KLRA*02 transcription levels contrasted in response to cytokine stimulation, whereas homozygous animals consistently transcribed higher levels of KLRA, regardless of the allele lineage. To assess the potential functional impact of KLRA diversity, we analyzed the relative NK cell mRNA expression of both allele lineages within and between individuals with different KLRA genotypes under cytokine stimuli. The two divergent allele lineages of cattle KLRA are the products of a single locus Cattle contain a unique and expanded NK cell receptor gene repertoire that creates diversity in the NK cell population.

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