The B7 Homolog Butyrophilin BTN2A1 Is a Novel Ligand for DC-SIGN

Malcherek, Georg; Mayr, Luzia; Roda-Navarro, Pedro; Rhodes, David A.; Miller, Nigel; Trowsdale, John

doi:10.4049/jimmunol.179.6.3804

Cited by 50 publications

(54 citation statements)

References 26 publications

(39 reference statements)

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“…1A), with very low levels of the transcript evident in other tissues as observed for Btn1a1. These results are similar to our previous studies on the orthologous human BTN2A1 gene where the transcript was detected in all tissues (30).…”

Section: Expression Of Btn1a1 and Btn2a2supporting

confidence: 82%

“…Multiple bands were observed in DCs, indicating possible modification or differential splicing. Our findings reflect those for human BTN2A1 (30) and BTN3A1 (29), for which expression of BTN protein was detected on lymphoid and myeloid cells from peripheral blood.…”

Section: Expression Of Btn1a1 and Btn2a2supporting

confidence: 71%

“…Recombinant human BTN3A1 protein binds to B and T cell lines (29), and similar experiments with human BTN2A1 revealed that a particular glycoform of BTN2A1 binds to a lectin molecule, DC-SIGN, found on dendritic cells (DCs) (30). Binding of BTN2A1 to DC-SIGN is dependent on high-mannose glycosylation of the protein when expressed by tumor cells.…”

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confidence: 99%

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BTN1A1, the Mammary Gland Butyrophilin, and BTN2A2 Are Both Inhibitors of T Cell Activation

Smith

Knezevic

Ammann

et al. 2010

The Journal of Immunology

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115

124

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Butyrophilin (BTN) genes encode a set of related proteins. Studies in mice have shown that one of these, BTN1A1, is required for milk lipid secretion in lactation, whereas butyrophilin-like 2 is a coinhibitor of T cell activation. To understand these disparate roles of BTNs, we first compared the expression and functions of mouse Btn1a1 and Btn2a2. Btn1a1 transcripts were not restricted to lactating mammary tissue but were also found in virgin mammary tissue and, interestingly, spleen and thymus. In confirmation of this, BTN1A1 protein was detected in thymic epithelial cells. By contrast, Btn2a2 transcripts and protein were broadly expressed. Cell surface BTN2A2 protein, such as the B7 family molecule programmed death ligand 1, was upregulated upon activation of T cells. We next examined the potential of both BTN1A1 and BTN2A2 to interact with T cells. Recombinant Fc fusion proteins of murine BTN2A2 and, surprisingly BTN1A1, bound to activated T cells, suggesting the presence of one or more receptors on these cells. Immobilized BTN-Fc fusion proteins, but not MOG-Fc protein, inhibited the proliferation of CD4 and CD8 T cells activated by anti-CD3. BTN1A1 and BTN2A2 also inhibited T cell metabolism, IL-2, and IFN-γ secretion. Inhibition of proliferation was not abrogated by exogenous IL-2 but could be overcome following costimulation with high levels of anti-CD28 Ab. These data are consistent with a coinhibitory role for mouse BTNs, including BTN1A1, the BTN expressed in the lactating mammary gland and on milk lipid droplets.

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Section: Expression Of Btn1a1 and Btn2a2supporting

confidence: 82%

Section: Expression Of Btn1a1 and Btn2a2supporting

confidence: 71%

See 1 more Smart Citation

BTN1A1, the Mammary Gland Butyrophilin, and BTN2A2 Are Both Inhibitors of T Cell Activation

Smith

Knezevic

Ammann

et al. 2010

The Journal of Immunology

Self Cite

115

124

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“…These experiments also revealed that a particular glycosylated form of BTN2A1 binds a lectin molecule, DC-SIGN, found on DCs, confirming the involvement of the BTN family as co-regulators of the immune system [10]. Furthermore, the binding of human BTN2A1 to DC-SIGN was also dependent on heavy glycosylation of the receptor when expressed by tumor cells.…”

Section: Introductionsupporting

confidence: 49%

Differential role for CD277 as a co‐regulator of the immune signal in T and NK cells

et al. 2011

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The human butyrophilin (BTN) 3 or CD277 molecules belong to the B7 family members and are expressed in various immune cells such as T and NK cells. Here, we show that CD277 triggering considerably enhances TCR-induced cytokine production and cell proliferation, even when another co-stimulatory molecule, CD28, is engaged. These CD277-induced additive functional effects are in accordance with the detection of early T-cell activation events such as TCR-induced cell signaling being increased upon CD277 engagement. However, we found that CD277 triggering is not involved in CD16-or NKp46-induced NK cell activation. BTN3/CD277 comprises three structurally related members, BTN3A1, BTN3A2 and BTN3A3. CD277 antibodies recognize all isoforms and we describe a differential expression of BTN3 isoforms between T and NK cells that could explain differential CD277 functions between T and NK cells. Our results show that, while T cells express all BTN3/CD277 transcripts, NK cells express mostly BTN3A2, which lacks the B30.2 intracellular domain. Furthermore, NKp30-induced cytokine production is decreased by the specific engagement of BTN3A2, but not by BTN3A1 triggering. Thus, we provide new insights into the CD277 co-stimulatory pathway that may differentially participate in the regulation of various cell-mediated immune responses.

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“…BTN2A1 is highly expressed by endothelial cells and can also be found in several tissues. DC-SIGN has been reported to be a binding partner for BTN2A1 (7), which allows the interaction with monocyte-derived DCs. BTN3 gene, which is only present in humans and not in mouse, is widely expressed in immune cells, such as T cells, B cells, NK cells, monocytes, and DCs (8).…”

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confidence: 99%

A Butyrophilin Family Member Critically Inhibits T Cell Activation

Yamazaki¹,

Goya

Graf

et al. 2010

The Journal of Immunology

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The costimulatory molecules in the B7-CD28 families are important in the regulation of T cell activation and tolerance. The butyrophilin family of proteins shares sequence and structure homology with B7 family molecules; however, the function of the butyrophilin family in the immune system has not been defined. In this study, we performed an analysis on multiple butyrophilin molecules and found that butyrophilin-like (BTNL)1 molecule functions to dampen T cell activation. BTNL1 mRNA was broadly expressed, but its protein was only found in APCs and not T cells. The putative receptor for BTNL1 was found on activated T cells and APCs. Also, recombinant BTNL1 molecule inhibited T cell proliferation by arresting cell cycle progression. The administration of neutralizing Abs against BTNL1 provoked enhanced T cell activation and exacerbated disease in autoimmune and asthma mouse models. Therefore, BTNL1 is a critical inhibitory molecule for T cell activation and immune diseases.

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The B7 Homolog Butyrophilin BTN2A1 Is a Novel Ligand for DC-SIGN

Cited by 50 publications

References 26 publications

BTN1A1, the Mammary Gland Butyrophilin, and BTN2A2 Are Both Inhibitors of T Cell Activation

BTN1A1, the Mammary Gland Butyrophilin, and BTN2A2 Are Both Inhibitors of T Cell Activation

Differential role for CD277 as a co‐regulator of the immune signal in T and NK cells

A Butyrophilin Family Member Critically Inhibits T Cell Activation

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