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

Smith, Isobel A.; Knezevic, Brittany R.; Ammann, Johannes U.; Rhodes, David A.; Aw, Danielle; Palmer, Donald B.; Mather, Ian H.; Trowsdale, John

doi:10.4049/jimmunol.0900416

Cited by 115 publications

(138 citation statements)

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“…The identification of these B30.2 interactors will be necessary to dissect the immunoregulatory mechanisms associated with the engagement of BTN3/CD277 molecule at the surface of T cells versus NK cells. Smith et al demonstrated that BTN1A1 and BTN2A2-Fc fusion proteins bound to activated T cells [22]. Immobilized BTN1A1 and BTN2A2-Fc fusion proteins inhibit the proliferation of murine CD4 1 …”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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 butyrophilins are part of the immunoglobulin superfamily and contain two folded immunoglobulin domains, a transmembrane domain and a C-terminal end that may include a large B30.2 domain. In addition to its role in the MFGM, butyrophilin1A1 has been found to be expressed within the thymus; other butyrophilins are more widely expressed among tissues (Smith et al, 2010a). Butyrophilins and related proteins of the immunoglobulin superfamily appear to play a role in the regulation of proliferation, cytokine secretion and activity of T-cells, and butyrophilin1A1 retains this function, at least in vitro (Smith et al, 2010a).…”

Section: Caseinsmentioning

confidence: 99%

“…In addition to its role in the MFGM, butyrophilin1A1 has been found to be expressed within the thymus; other butyrophilins are more widely expressed among tissues (Smith et al, 2010a). Butyrophilins and related proteins of the immunoglobulin superfamily appear to play a role in the regulation of proliferation, cytokine secretion and activity of T-cells, and butyrophilin1A1 retains this function, at least in vitro (Smith et al, 2010a). It is interesting that butyrophilin1A1 is the only butyrophilin that appears to bind XOR via its B30.2 domain, and it is this binding that is believed to be critical to MFG secretion from lactocytes (Jeong et al, 2009).…”

Section: Caseinsmentioning

confidence: 99%

The evolution of milk secretion and its ancient origins

Oftedal

2012

Animal

196

142

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Lactation represents an important element of the life history strategies of all mammals, whether monotreme, marsupial, or eutherian. Milk originated as a glandular skin secretion in synapsids (the lineage ancestral to mammals), perhaps as early as the Pennsylvanian period, that is, approximately 310 million years ago (mya). Early synapsids laid eggs with parchment-like shells intolerant of desiccation and apparently dependent on glandular skin secretions for moisture. Mammary glands probably evolved from apocrine-like glands that combined multiple modes of secretion and developed in association with hair follicles. Comparative analyses of the evolutionary origin of milk constituents support a scenario in which these secretions evolved into a nutrient-rich milk long before mammals arose. A variety of antimicrobial and secretory constituents were co-opted into novel roles related to nutrition of the young. Secretory calcium-binding phosphoproteins may originally have had a role in calcium delivery to eggs; however, by evolving into large, complex casein micelles, they took on an important role in transport of amino acids, calcium and phosphorus. Several proteins involved in immunity, including an ancestral butyrophilin and xanthine oxidoreductase, were incorporated into a novel membrane-bound lipid droplet (the milk fat globule) that became a primary mode of energy transfer. An ancestral c-lysozyme lost its lytic functions in favor of a role as a-lactalbumin, which modifies a galactosyltransferase to recognize glucose as an acceptor, leading to the synthesis of novel milk sugars, of which free oligosaccharides may have predated free lactose. An ancestral lipocalin and an ancestral whey acidic protein four-disulphide core protein apparently lost their original transport and antimicrobial functions when they became the whey proteins b-lactoglobulin and whey acidic protein, which with a-lactalbumin provide limiting sulfur amino acids to the young. By the late Triassic period (ca 210 mya), mammaliaforms (mammalian ancestors) were endothermic (requiring fluid to replace incubatory water losses of eggs), very small in size (making large eggs impossible), and had rapid growth and limited tooth replacement (indicating delayed onset of feeding and reliance on milk). Thus, milk had already supplanted egg yolk as the primary nutrient source, and by the Jurassic period (ca 170 mya) vitellogenin genes were being lost. All primary milk constituents evolved before the appearance of mammals, and some constituents may have origins that predate the split of the synapsids from sauropsids (the lineage leading to 'reptiles' and birds). Thus, the modern dairy industry is built upon a very old foundation, the cornerstones of which were laid even before dinosaurs ruled the earth in the Jurassic and Cretaceous periods.Keywords: evolution, lactation, milk composition, casein, milk fat globule ImplicationsLactation has an evolutionary origin and biological context within which its secretory processes and milk constituents evolved. This revi...

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“…BTN1A1 is predominately expressed in mammary gland and at low levels can be detected in several tissues, such as spleen, thymus, small intestine, and so forth (6). BTN2A2 is broadly expressed in lymphoid and nonlymphoid organs, and both BTN1A1 and BTN2A2 are expressed by thymic stromal cells (6).…”

mentioning

confidence: 99%

“…The BTN2 and BTN3 groups comprise three genes each: BTN2A1, BTN2A2, BTN2A3 and BTN3A1, BTN3A2, BTN3A3, respectively (6).…”

mentioning

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

Cited by 115 publications

References 50 publications

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

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

The evolution of milk secretion and its ancient origins

A Butyrophilin Family Member Critically Inhibits T Cell Activation

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