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

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Abstract Unlike αβ T cells, γδ T cells respond to a variety non-proteinaceous molecules independent of MHC presentation. γδ T cells are less susceptible to immune evasion, making them an attractive target for next generation vaccines, however, little is known about the best way to prime them. WC1, a member of the group B Scavenger Receptor Cysteine Rich (SRCR) superfamily, is expressed exclusively on γδ T cells in swine and ruminants. Previous work in our lab has determined that there are 13 genes encoding for WC1 in cattle. We have also shown that WC1 functions as hybrid co-receptor and pattern recognition receptor for the γδ TCR. WC1+ γδ T cells share a restriction in 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 recognize and 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. Swine belong to the same order as cattle, Artiodactyl, and are susceptible to infection with many of the same pathogens. The current swine assembly contains two predicted WC1 proteins, neither of which had been confirmed with cDNA evidence. Prior to this study only one full-length cDNA transcript had been successfully amplified. Using 5′/3′ RACE PCR and RT-PCR, we have obtained full length cDNA transcripts for seven WC1 genes with the SRCR domain patterns of a1-[b-c-d-e-d′] or d1-[b-c-d-e-d′]. Through bacterial pull-down assays, we have shown that multiple SRCR domains from different swine WC1 genes bind to vaccine strain Leptospira spp, and freshly grown Pasteur and Danish strains of Mycobacterium bovis.