Genomic organization and classification of the bovine WC1 genes and expression by peripheral blood gamma delta T cells

Herzig, Carolyn T.A.; Baldwin, Cynthia L.

doi:10.1186/1471-2164-10-191

Cited by 50 publications

(78 citation statements)

References 65 publications

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“…WC1 transcripts are extensively alternatively spliced (40), which may be a mechanism to modulate ligation by bacteria. All the assays shown here used a 1 nM concentration of the individual SRCR domains, suggesting that the affinity of WC1 for its ligands is high, although this remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…WC1 transcripts are extensively alternatively spliced, including the splicing out of the exon encoding the transmembrane domain, which would be predicted to result in a soluble secreted molecule like DMBT1 (40). We observed toxic effects of some WC1 SRCR domains on E. coli during cloning, presumably from low-level expression inside the bacteria, and we investigated whether incubation with WC1 SRCR domains could affect the growth of Leptospira spp.…”

Section: Srcr Domain Inhibits Leptospira Spp Growth In a Binding-depmentioning

confidence: 99%

“…In addition, there is precedent for a multigenic array of SRCR domain-containing proteins lending diversity to the immune response in the purple sea urchin Strongylocentrotus purpuratus, whose genome contains ∼200 SRCR genes whose expression changes upon challenge with bacteria (36)(37)(38). The 13 diverse bovine WC1 open reading frames conserved among cattle could act as hybrid coreceptors and pattern recognition receptors adding specificity and diversity to a relatively restricted gd TCR repertoire, since collectively the 13 WC1 molecules have 138 SRCR domains (39,40).…”

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confidence: 99%

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WC1 Is a Hybrid γδ TCR Coreceptor and Pattern Recognition Receptor for Pathogenic Bacteria

Hsu

Chen

Nenninger

et al. 2015

The Journal of Immunology

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Srcr Domain Inhibits Leptospira Spp Growth In a Binding-depmentioning

confidence: 99%

mentioning

confidence: 99%

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WC1 Is a Hybrid γδ TCR Coreceptor and Pattern Recognition Receptor for Pathogenic Bacteria

Hsu

Chen

Nenninger

et al. 2015

The Journal of Immunology

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“…To highlight the potential evolutionary contributions of these CNVs to cattle breed formation and adaptation, we conservatively queried out 35 CNVRs that have high-confidence breed-specific CNV frequency differences (Supplemental Table S12). Twenty-nine of these CNVRs correspond to annotated genes or gene families, while many of them are also known in other mammals to interact with environments, some of them are known to be important in cattle adaptation including SCP2 (Liu et al 2009), ULBP (Larson et al 2006), and WC1.1 (Herzig and Baldwin 2009). To our knowledge, this is the first systematic report on breed-specific copy number differences in cattle.…”

Section: Cattle Cnv Frequency Differences Among Breedsmentioning

confidence: 99%

Analysis of copy number variations among diverse cattle breeds

Liu¹,

Hou²,

Zhu³

et al. 2010

Genome Res.

264

318

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Genomic structural variation is an important and abundant source of genetic and phenotypic variation. Here, we describe the first systematic and genome-wide analysis of copy number variations (CNVs) in modern domesticated cattle using array comparative genomic hybridization (array CGH), quantitative PCR (qPCR), and fluorescent in situ hybridization (FISH). The array CGH panel included 90 animals from 11 Bos taurus, three Bos indicus, and three composite breeds for beef, dairy, or dual purpose. We identified over 200 candidate CNV regions (CNVRs) in total and 177 within known chromosomes, which harbor or are adjacent to gains or losses. These 177 high-confidence CNVRs cover 28.1 megabases or ;1.07% of the genome. Over 50% of the CNVRs (89/177) were found in multiple animals or breeds and analysis revealed breed-specific frequency differences and reflected aspects of the known ancestry of these cattle breeds. Selected CNVs were further validated by independent methods using qPCR and FISH. Approximately 67% of the CNVRs (119/177) completely or partially span cattle genes and 61% of the CNVRs (108/177) directly overlap with segmental duplications. The CNVRs span about 400 annotated cattle genes that are significantly enriched for specific biological functions, such as immunity, lactation, reproduction, and rumination. Multiple gene families, including ULBP, have gone through ruminant lineage-specific gene amplification. We detected and confirmed marked differences in their CNV frequencies across diverse breeds, indicating that some cattle CNVs are likely to arise independently in breeds and contribute to breed differences. Our results provide a valuable resource beyond microsatellites and single nucleotide polymorphisms to explore the full dimension of genetic variability for future cattle genomic research.

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“…WC1-expressing subsets contribute to the M. bovis-specific gd T cell response in cattle There are 13 WC1 genes whose distribution defines unique subsets of bovine gd T cells (25,26). Although several subpopulations exist, serologically, gd T cells can only be divided into three major subsets: WC1.1 + , WC1.2 + , and WC1.3 + .…”

Section: Bovine Gd T Cells From Virulent M Bovis-infected Animals Rementioning

confidence: 99%

Specific Recognition of Mycobacterial Protein and Peptide Antigens by γδ T Cell Subsets following Infection with VirulentMycobacterium bovis

McGill

Sacco

Baldwin

et al. 2014

The Journal of Immunology

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Promoting effective immunity to Mycobacterium bovis infection is a challenge that is of interest to the fields of human and animal medicine alike. We report that γδ T cells from virulent M. bovis–infected cattle respond specifically and directly to complex, protein, and nonprotein mycobacterial Ags. Importantly, to our knowledge, we demonstrate for the first time that bovine γδ T cells specifically recognize peptide Ags derived from the mycobacterial protein complex ESAT6:CFP10 and that this recognition requires direct contact with APCs and signaling through the T cell Ag receptor but is independent of MHC class I or II. Furthermore, we show that M. bovis infection in cattle induces robust IL-17A protein responses. Interestingly, in contrast to results from mice, bovine CD4 T cells, and not γδ T cells, are the predominant source of this critical proinflammatory mediator. Bovine γδ T cells are divided into subsets based upon their expression of Workshop Cluster 1 (WC1), and we demonstrate that the M. bovis–specific γδ T cell response is composed of a heterogeneous mix of WC1-expressing populations, with the serologically defined WC1.1+ and WC1.2+ subsets responding in vitro to mycobacterial Ags and accumulating in the lesions of M. bovis–infected animals. The results described in this article enhance our understanding of γδ T cell biology and, because virulent M. bovis infection of cattle represents an excellent model of tuberculosis in humans, contribute to our overall understanding of the role of γδ T cells in the mycobacterial-specific immune response.

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Genomic organization and classification of the bovine WC1 genes and expression by peripheral blood gamma delta T cells

Cited by 50 publications

References 65 publications

WC1 Is a Hybrid γδ TCR Coreceptor and Pattern Recognition Receptor for Pathogenic Bacteria

WC1 Is a Hybrid γδ TCR Coreceptor and Pattern Recognition Receptor for Pathogenic Bacteria

Analysis of copy number variations among diverse cattle breeds

Specific Recognition of Mycobacterial Protein and Peptide Antigens by γδ T Cell Subsets following Infection with VirulentMycobacterium bovis

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