Annotation of the WC1 gene family in Sus scrofa and evaluation of individual SRCR domain affinity for Mycobacterium bovis and Leptospira spp

Abstract

Abstract γδ T cells respond to a variety of proteins and non-proteinaceous molecules independent of MHC presentation, making them less susceptible to immune evasion and thus; an attractive target for next-generation vaccines. Unfortunately, definitive methods to prime these cells remain elusive. WC1, a member of the group B Scavenger Receptor Cysteine-Rich (SRCR) superfamily, is expressed exclusively on the γδ T cells of swine and ruminants and functions as hybrid co-receptor and pattern recognition receptor for the γδ TCR. It is known that there are thirteen unique WC1 genes expressed in cattle, each containing up to eleven extracellular SRCR domains. Bovine WC1+ γδ T cells share restriction in their TCR gene usage, yet respond to different pathogens based on which WC1 molecule(s) they express. This can be attributed to the ability of the expressed WC1 molecule to directly bind whole pathogens via its SRCR domains. Because WC1 is expressed as a multigene array, we hypothesize that each WC1 gene has co-evolved with a different set of pathogens, and may be exploited to generate a protective immune response from WC1+ γδ T-cells. We sought to identify and characterize WC1 genes expressed in swine, and evaluate their pathogen binding potential. We have obtained cDNA evidence for ten swine WC1 genes, containing up to six extracellular SRCR domains. Through annotation with MAKER, we have confirmed the presence of seven of these genes in the current assembly, Sus scrofa 11.1, and identified four unique exon-intron gene structures. We have shown that SRCR domains from multiple WC1 genes differentially bind Leptospira spp, and Mycobacterium bovis BCG Danish and Pasteur strains.