Abstract

Natural killer (NK) cells have important functions in immunity. NK recognition in mammals can be mediated through killer cell immunoglobulin-like receptors (KIR) and/or killer cell lectin-like Ly49 receptors. Genes encoding highly variable NK cell receptors (NKR) represent rapidly evolving genomic regions. No single conservative model of NKR genes was observed in mammals. Single-copy low polymorphic NKR genes present in one mammalian species may expand into highly polymorphic multigene families in other species. In contrast to other non-rodent mammals, multiple Ly49-like genes appear to exist in the horse, while no functional KIR genes were observed in this species. In this study, Ly49 and KIR were sought and their evolution was characterized in the entire family Equidae. Genomic sequences retrieved showed the presence of at least five highly conserved polymorphic Ly49 genes in horses, asses and zebras. These findings confirmed that the expansion of Ly49 occurred in the entire family. Several KIR-like sequences were also identified in the genome of Equids. Besides a previously identified non-functional KIR-Immunoglobulin-like transcript fusion gene (KIR-ILTA) and two putative pseudogenes, a KIR3DL-like sequence was analyzed. In contrast to previous observations made in the horse, the KIR3DL sequence, genomic organization and mRNA expression suggest that all Equids might produce a functional KIR receptor protein molecule with a single non-mutated immune tyrosine-based inhibition motif (ITIM) domain. No evidence for positive selection in the KIR3DL gene was found. Phylogenetic analysis including rhinoceros and tapir genomic DNA and deduced amino acid KIR-related sequences showed differences between families and even between species within the order Perissodactyla. The results suggest that the order Perissodactyla and its family Equidae with expanded Ly49 genes and with a potentially functional KIR gene may represent an interesting model for evolutionary biology of NKR genes.

Highlights

  • Natural killer (NK) cells have complex biological functions in both innate and adaptive immunity

  • NK recognition in mammals can be mediated through highly variable killer cell immunoglobulin-like receptors (KIR) and/or killer cell lectin-like Ly49 receptors

  • The structure of the LY49 genomic region and its high sequence similarity to the rodent models suggested that Ly49 receptors might be fully functional in this mammalian group

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Summary

Introduction

Natural killer (NK) cells have complex biological functions in both innate and adaptive immunity They can recognize and subsequently eliminate microbe-infected and/or tumor cells, but they have positive or negative influence on host T and B cell immunity. Killer immunoglobulin-like receptors (KIRs) expressed on NK cells bind major histocompatibility complex (MHC) class I ligands. The Ly49 family encodes C-type lectinlike Ly49 molecules interacting with classical MHC class I molecules, due probably to convergent evolution This component of immune responses is very dynamic, subject to varying selection pressures [2]. Single-copy low polymorphic NKR genes present in one mammalian species may expand into highly polymorphic multigene families in other species [5]

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