Scavenger receptor WC1 contributes to the γδ T cell response to Leptospira

Wang, Fei; Herzig, Carolyn T.A.; Chen, Chuang; Hsu, Haoting; Baldwin, Cynthia L.; Telfer, Janice C.

doi:10.1016/j.molimm.2010.12.001

Cited by 43 publications

(42 citation statements)

References 64 publications

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“…We report in this article the accumulation of WC1.1 + and WC1.2 + gd T cells within the pulmonary granulomatous lesions of M. bovis-infected animals, as well as responses by both subsets in vitro. A recent report by Wang et al (21) demonstrates that expression of gene products encoding for WC1.1, specifically genes WC1-1, WC1-3, and WC1-2, is necessary for the Ag-specific activation of gd T cells by Leptospira, suggesting that WC1 is acting as a PRR similar to TLRs. From these results, one can infer that different WC1 molecules are binding specific microbial products; thus, differential expression of WC1 can contribute to determining the Ag-specific activation of the cell.…”

Section: Discussionmentioning

confidence: 99%

“…Together, our results suggest that bovine gd T cells respond specifically to both whole recombinant E:C protein and the peptides derived from it and that this recognition requires direct cell-cell contact with an APC and signaling through the gd TCR but is independent of Ag presentation via MHC class I or II. Both WC1.1 + and WC1.2 + gd T cells respond to M. bovis WC1 has been hypothesized to act as a PRR on bovine gd T cells, binding pathogen components and lending specificity or amplification to TCR-mediated Ag recognition (21). In support of this, the serologically defined WC1.1 + gd T cell subpopulation responds specifically to Leptospira, and WC1 plays a direct role in this recall response (29,30), whereas the serologically defined WC1.2 + gd T cell subpopulation responds specifically to infection with A. marginale (48).…”

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

confidence: 99%

“…Functionally, recent reports (21) suggest that WC1 molecules act as pattern recognition receptors (PRRs) on gd T cells, similar to TLR. WC1 + gd T cells are CD2 2 CD8 2 and are the predominant subset in circulation, whereas WC1 2 gd T cells are CD2 + CD8 + and are prevalent in tissues such as the spleen, intestinal mucosa, and mesenteric LNs (22)(23)(24).…”

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confidence: 99%

“…WC1.1 + gd T cells are proinflammatory and produce IFN-g in response to Leptospira borgpetersenii (21,29,30), whereas the WC1.2 + gd T cell subset produces little IFN-g in response to mitogen stimulation but substantial amounts of IL-10 and can suppress CD4 T cell proliferation (31,32). Interestingly, however, WC1.2 + gd T cells produce IFN-g in specific response to the bovine rickettsial pathogen Anaplasma marginale (33), suggesting that this subset has some functional plasticity that may be dependent upon PRR stimulation with the TCR.…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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

confidence: 99%

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confidence: 99%

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confidence: 99%

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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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“…Following activation, WC1 colocalizes with the gd TCR-CD3 complex in lipid rafts (22). Knockdown of some WC1 gene products significantly decreases gd T cell responses to Leptospira (23), suggesting that individual WC1 molecules have the capacity to determine whether a restricted set of g or d TCR is activated by bacterial pathogens. WC1 + gd T cells are divided into subpopulations known as WC1.1 + and WC1.2 + based on expression of a specific set of WC1 genes (20).…”

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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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Lymphocyte Biology and Functions

Tizard¹

2022

Schalm's Veterinary Hematology

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Scavenger receptor WC1 contributes to the γδ T cell response to Leptospira

Cited by 43 publications

References 64 publications

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

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

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

Lymphocyte Biology and Functions

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