| Structural highlights
Function
[BT3A1_HUMAN] Plays a role in T-cell activation and in the adaptive immune response. Regulates the proliferation of activated T-cells. Regulates the release of cytokines and IFNG by activated T-cells. Mediates the response of T-cells toward infected and transformed cells that are characterized by high levels of phosphorylated metabolites, such as isopentenyl pyrophosphate.[1] [2] [3] [4]
Publication Abstract from PubMed
The three butyrophilin BTN3A molecules, BTN3A1, BTN3A2, and BTN3A3, are members of the B7/butyrophilin-like group of Ig superfamily receptors, which modulate the function of T cells. BTN3A1 controls activation of human Vgamma9/Vdelta2 T cells by direct or indirect presentation of self and nonself phosphoantigens (pAg). We show that the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate binds to the intracellular B30.2 domain of BTN3A1 with an affinity of 1.1 muM, whereas the endogenous pAg isopentenyl pyrophosphate binds with an affinity of 627 muM. Coculture experiments using knockdown cell lines showed that in addition to BTN3A1, BTN3A2 and BTN3A3 transmit activation signals to human gammadelta T cells in response to (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate and the aminobisphosphonate drug zoledronate that causes intracellular accumulation of isopentenyl pyrophosphate. The plakin family member periplakin, identified in yeast two-hybrid assays, interacted with a membrane-proximal di-leucine motif, located proximal to the B30.2 domain in the BTN3A1 cytoplasmic tail. Periplakin did not interact with BTN3A2 or BTN3A3, which do not contain the di-leucine motif. Re-expression into a BTN3A1 knockdown line of wild-type BTN3A1, but not of a variant lacking the periplakin binding motif, BTN3A1Deltaexon5, restored gammadelta T cell responses, demonstrating a functional role for periplakin interaction. These data, together with the widespread expression in epithelial cells, tumor tissues, and macrophages detected using BTN3A antiserum, are consistent with complex functions for BTN3A molecules in tissue immune surveillance and infection, linking the cell cytoskeleton to gammadelta T cell activation by indirectly presenting pAg to the Vgamma9/Vdelta2 TCR.
Activation of human gammadelta T cells by cytosolic interactions of BTN3A1 with soluble phosphoantigens and the cytoskeletal adaptor periplakin.,Rhodes DA, Chen HC, Price AJ, Keeble AH, Davey MS, James LC, Eberl M, Trowsdale J J Immunol. 2015 Mar 1;194(5):2390-8. doi: 10.4049/jimmunol.1401064. Epub 2015 Jan, 30. PMID:25637025[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ Messal N, Mamessier E, Sylvain A, Celis-Gutierrez J, Thibult ML, Chetaille B, Firaguay G, Pastor S, Guillaume Y, Wang Q, Hirsch I, Nunes JA, Olive D. Differential role for CD277 as a co-regulator of the immune signal in T and NK cells. Eur J Immunol. 2011 Dec;41(12):3443-54. doi: 10.1002/eji.201141404. Epub 2011 Nov, 3. PMID:21918970 doi:10.1002/eji.201141404
- ↑ Harly C, Guillaume Y, Nedellec S, Peigne CM, Monkkonen H, Monkkonen J, Li J, Kuball J, Adams EJ, Netzer S, Dechanet-Merville J, Leger A, Herrmann T, Breathnach R, Olive D, Bonneville M, Scotet E. Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human gammadelta T-cell subset. Blood. 2012 Sep 13;120(11):2269-79. doi: 10.1182/blood-2012-05-430470. Epub 2012 , Jul 5. PMID:22767497 doi:10.1182/blood-2012-05-430470
- ↑ Palakodeti A, Sandstrom A, Sundaresan L, Harly C, Nedellec S, Olive D, Scotet E, Bonneville M, Adams EJ. The molecular basis for modulation of human Vgamma9Vdelta2 T cell responses by CD277/butyrophilin-3 (BTN3A)-specific antibodies. J Biol Chem. 2012 Sep 21;287(39):32780-90. Epub 2012 Jul 30. PMID:22846996 doi:10.1074/jbc.M112.384354
- ↑ Rhodes DA, Chen HC, Price AJ, Keeble AH, Davey MS, James LC, Eberl M, Trowsdale J. Activation of human gammadelta T cells by cytosolic interactions of BTN3A1 with soluble phosphoantigens and the cytoskeletal adaptor periplakin. J Immunol. 2015 Mar 1;194(5):2390-8. doi: 10.4049/jimmunol.1401064. Epub 2015 Jan, 30. PMID:25637025 doi:http://dx.doi.org/10.4049/jimmunol.1401064
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