title: WC1 is a hybrid γδ TCR coreceptor and pattern recognition receptor for pathogenic bacteria.
abstract: 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). 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. We hypothesized that individual WC1 receptors encode Ag specificity via coligation of bacteria with the γδ TCR. SRCR domain binding was 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. Three to five of eleven WC1-3 SRCR domains, but none of the eleven WC1-4 SRCR domains, interacted with Leptospira spp. and Borrelia burgdorferi, but not with Escherichia coli or Staphylococcus aureus. Mutational analysis indicated that the active site for bacterial binding in one of the SRCR domains is composed of amino acids in three discontinuous regions. Recombinant WC1 SRCR domains with the ability to bind leptospires inhibited Leptospira growth. Our data suggest that WC1 gene arrays play a multifaceted role in the γδ T cell response to bacteria, including acting as hybrid pattern recognition receptors and TCR coreceptors, and they may function as antimicrobials.
authors: Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003; and Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA 01003.
authors: Haoting
authors: H
authors: Hsu
authors: Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003; and Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA 01003.
authors: Chuang
authors: C
authors: Chen
authors: Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003; and.
authors: Ariel
authors: A
authors: Nenninger
authors: Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003; and.
authors: Lauren
authors: L
authors: Holz
authors: Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003; and Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA 01003.
authors: Cynthia L
authors: CL
authors: Baldwin
authors: Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003; and Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA 01003 telfer@vasci.umass.edu.
authors: Janice C
authors: JC
authors: Telfer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D025065:Borrelia burgdorferi / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity; D002417:Cattle; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D007919:Leptospira / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity; D007921:Leptospira interrogans / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D013211:Staphylococcus aureus / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
chemical_list: C086500:DMBT1 protein, Bos taurus; D008562:Membrane Glycoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011994:Recombinant Proteins