Oral Presentation International Veterinary Immunology Symposium 2016

WC1 is a Hybrid gammadelta TCR Coreceptor and Pattern Recognition Receptor for Pathogenic Bacteria. (#35)

Janice C Telfer 1 , Lauren LePage 1 , Alexandra Gillespie 1 , Payal Yokota 1 , Cynthia L Baldwin
  1. University of Massachusetts Amherst, Amherst, MA, United States

WC1 proteins are uniquely expressed on γδ T cells and belong to the scavenger receptor cysteine-rich (SRCR) superfamily. While present in variable, and sometimes high, numbers in the genomes of mammals and birds, in cattle there are 13 distinct genes (WC1-1 to WC1-13). The structure of a multigenic WC1 gene array, with each WC1 protein containing multiple SRCR domains in its extracellular domain, has been conserved over millions of years of evolutionary time, suggesting that they act as a panel of pattern recognition receptors for conserved pathogen ligands. All bovine WC1 proteins can serve as coreceptors for the TCR in a tyrosine phosphorylation dependent manner and some are required for the γδ T cell response to Leptospira. SRCR domain binding is directly correlated with γδ T cell response, as WC1-3 SRCR domains from Leptospira-responsive cells, but not WC1-4 SRCR domains from Leptospira-nonresponsive cells, bound to multiple serovars of two Leptospira species, L. borgpetersenii and L. interrogans. Mutational analysis indicated that the active site for bacterial binding in one of the SRCR domains is comprised of amino acids in three discontinuous regions. In addition, recombinant WC1 SRCR domains with the ability to bind leptospires inhibited Leptospira growth. WC1 SRCR domains also bind to Borrelia burgdorferi and Mycobacterium spp. WC1 in other artiodactyls such as goat, sheep and swine are closely related, but show some divergence that may have been driven by natural selection by species-specific pathogens. Our data suggest that WC1 gene arrays play a multi-faceted role in the γδ T cell response to bacteria in multiple species, including acting as hybrid pattern recognition receptors and TCR coreceptors, and may function as anti-microbials.