Characterization of WC1 co-receptors on functionally distinct subpopulations of ruminant γδ T cells

Rogers, Aric N.; VanBuren, Denille G.; Zou, Bai-Xiang; Lahmers, Kevin K.; Herzig, Carolyn T.A.; Brown, Wendy C.; Telfer, Janice C.; Baldwin, Cynthia L.

doi:10.1016/j.cellimm.2006.05.006

Cited by 26 publications

(27 citation statements)

References 34 publications

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“…That is, ligation of WC1 with antibody induces dephosphorylation of a wide range of cell cycle regulatory proteins and results in growth arrest [9][10][11], but anti-WC1 antibody also augments proliferation of gd T cells in the autologous mixed leukocyte reaction as well as proliferation induced by anti-CD3 antibody [12]. These data indicate that WC1 can have both positive and negative effects on gd T-cell activation, consistent with the effects of another SRCR family member found on lymphocytes, CD5 [13][14][15].Comparison of the cytoplasmic tails of the various WC1 forms reveals the presence of five tyrosines that could be potentially phosphorylated by the members of src family of protein -tyrosine kinases [16,17]. However, subtle sequence variations between WC1.1 and WC1.2 cytoplasmic tails [8,16] could affect intracellular signaling, and thus result in a different outcome following antigen or cytokine stimulation.…”

supporting

confidence: 69%

“…WC1.1 and WC1.2) have been found to be expressed on non-overlapping gd T-cell populations. cDNA encoding an archetypal full-length WC1.1 molecule ( [17], accession number X63723), fragments of archetypal WC1.2 cDNA including a complete cytoplasmic tail sequence, and additional tail sequences for variants of both WC1.1 and WC1.2 have been reported [16,18]. Although WC1 cDNA assigned to each group have variations in their cytoplasmic tail sequences, the sequence organization of WC1.1 and WC1.2 cDNA is more similar than those assigned to other WC1 groups, i.e.…”

Section: Antibody-mediated Crosslinking Increases the Phosphorylationmentioning

confidence: 99%

“…Comparison of the cytoplasmic tails of the various WC1 forms reveals the presence of five tyrosines that could be potentially phosphorylated by the members of src family of protein -tyrosine kinases [16,17]. However, subtle sequence variations between WC1.1 and WC1.2 cytoplasmic tails [8,16] could affect intracellular signaling, and thus result in a different outcome following antigen or cytokine stimulation.…”

mentioning

confidence: 99%

“…However, subtle sequence variations between WC1.1 and WC1.2 cytoplasmic tails [8,16] could affect intracellular signaling, and thus result in a different outcome following antigen or cytokine stimulation. In this study, we compared the potential of archetypal WC1.1 and WC1.2 to be phosphorylated in vivo and in vitro and determined the site of tyrosine phosphorylation in both the WC1.1 and WC1.2 cytoplasmic tail sequences.…”

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confidence: 99%

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Tyrosine phosphorylation of scavenger receptor cysteine‐rich WC1 is required for the WC1‐mediated potentiation of TCR‐induced T‐cell proliferation

et al. 2009

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Workshop cluster 1 (WC1) molecules are transmembrane glycoproteins uniquely expressed by cd T cells. They belong to the scavenger receptor cysteine-rich superfamily and are encoded by a multi-gene family, which is divided on the basis of antibody reactivity, into three groups, WC1.1, WC1.2, and WC1.3. The potential role of WC1 as a co-stimulatory molecule for the cd TCR is suggested by the presence of several tyrosinebased motifs in their intracellular domains. In this study, we found that WC1 was constitutively phosphorylated in ex vivo bovine cd T cells and associated with src family tyrosine kinases. Crosslinking of WC1 molecules resulted in an increase in WC1 phosphorylation and co-crosslinking of WC1 and cd TCR together prolonged WC1 phosphorylation. We identified the second tyrosine residue as the primary phosphorylation target in WC1.1 and WC1.2 intracellular sequences in both in vitro and in vivo assays. The cytoplasmic tails of WC1.1 and WC1.2 were phosphorylated on serine and PKC activity was required for PMA-induced endocytosis of WC1.1 or WC1.2. We found that phosphorylation of the second tyrosine in the WC1 cytoplasmic domain was required for the WC1-mediated potentiation of TCR-induced T-cell proliferation, suggesting that WC1 acts as a co-stimulatory molecule for cd TCR.Key words: Bovine . Cell surface molecules . gd T cells . Signal transduction IntroductionIn adult chickens, ruminants and pigs, unlike in mice and humans, gd T cells can constitute 30% of total PBMC [1]. A majority of these gd T cells in ruminants bear the glycoprotein lineage marker Workshop cluster 1 (WC1) on their surface. Based on the profiles of their gene expression, WC1 1 gd T cells of cattle represent the inflammatory population, whereas WC1 À gd T cells are regulatory cells [2,3]. WC1, a member of the scavenger receptor cysteine-rich (SRCR) superfamily, is categorized into group B along with CD5, CD6, and CD163, based on the organization of cysteine residues in its extracellular SRCR domains [4]. Like the SRCR family member SpSRCR, which is expressed in the immune cells of the purple sea urchin [5], WC1 molecules are products of a large gene family, and thus have the potential to increase the diversity of immune responses independently of the adaptive immune response receptor, i.e. the TCR.Bovine gd T cells express at least three known variants, WC1.1, WC1.2, and WC1.3, which are defined by antibodies recognizing unknown epitopes on their SRCR domains [6]. WC1.1 and WC1.2 are expressed on two mostly non-overlapping subsets of bovine gd T cells, and WC1.3 is expressed on a small 254subpopulation of WC1.1 1 cells. Cytokine production and cellular proliferation in response to stimulation vary according to the forms of WC1 expressed by gd T cells [7]. Ex vivo WC1.1 1 gd T cells, but not WC1.2 1 gd T cells, proliferate well to the gd T-cell antigens of Leptospira, and produce IFN-g in response to either antigen or 8].The correlation of the expression of a variable WC1 gene product with a cellular immune response to antigen su...

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supporting

confidence: 69%

Section: Antibody-mediated Crosslinking Increases the Phosphorylationmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Tyrosine phosphorylation of scavenger receptor cysteine‐rich WC1 is required for the WC1‐mediated potentiation of TCR‐induced T‐cell proliferation

et al. 2009

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“…+ gd T cells into the serologically defined subpopulations: WC1.1 + , WC1.2 + , and WC1.3 + (27,28). 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).…”

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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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TCR and CD3 antibody cross‐reactivity in 44 species

2007

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The production of monoclonal antibodies is very costly, and antibodies are only available for a limited number of species. Until a more cost effective method of antibody production is found, identification of cross-reactive antibodies is an alternative approach that can provide investigators studying immunity in minor species with valuable antibody reagents. Flow cytometry was used to test 21 monoclonal antibodies (mAb), raised against ab and gd T cell receptors and CD3 from human and five animal species, for cross-reactivity in 44 different species including 16 species of nonhuman primates, marsupials, carnivores, lagomorphs, rodents, ruminants, swine, cetacean, horse, birds, a reptile, and fish. Fifteen of the mAbs cross-reacted with orthologous molecules in one or more species. Two antibodies, anti-human TCR gd (B1.1), and anti-human CD3 (SP34) were found to costain in 13 species of nonhuman primates. This study has identified valuable new reagents for studying T cell populations in different animal species and for the first time characterized antibodies useful for studying gd T cell populations in many species of primates. These antibodies may be used for further immunity research in species with less well-characterized immune systems. ' 2007 International Society for Analytical Cytology Key terms monoclonal antibody; T cell receptor; ab; gd; CD3; WC1; cross-reactivity; primate; mammal; carnivore AN interesting finding to emerge from T cell research is the disparity between peripheral blood gd T cell populations in certain animals. Percentages of gd T lymphocytes in peripheral blood vary so greatly between different species that species can be classified as gd high or low (1). gd low species include humans and mice (2-5%) (2,3) and gd high species include chickens (15%) (4), swine (24%) (5), and cattle (20-40%) (6).The high concentration of gd T cells in ruminants and swine is attributable to the presence of a subpopulation of gd T cells that express the workshop cluster 1 (WC1) molecule in ruminants and the orthologue in swine. WC1 and orthologues have only been identified in artiodactyls including ruminants, swine, and camelids (7,8). The current data suggest this is a unique population of gd T cells that has evolved in artiodactyls. The concentration of WC1-gd T cells identified in ruminants and swine is similar to the concentration seen in humans and mice (9,10). Analysis of gd T cells in chickens has not revealed an explanation for the high concentration of gd T cells. The lack of reagents has thus far limited analysis of the composition and function of gd T cells in additional species. Identification of cross reactive mAbs would facilitate the conduct of further studies and an opportunity to delineate any functional differences in populations of gd T cells present in species with high and low concentrations of gd T cells in peripheral blood.Comparative studies with mAbs developed against major histocompatibility and leukocyte differentiation antigens in humans and other species have demonstr...

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Characterization of WC1 co-receptors on functionally distinct subpopulations of ruminant γδ T cells

Cited by 26 publications

References 34 publications

Tyrosine phosphorylation of scavenger receptor cysteine‐rich WC1 is required for the WC1‐mediated potentiation of TCR‐induced T‐cell proliferation

Tyrosine phosphorylation of scavenger receptor cysteine‐rich WC1 is required for the WC1‐mediated potentiation of TCR‐induced T‐cell proliferation

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

TCR and CD3 antibody cross‐reactivity in 44 species

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