ABCA1, apoA-I, and BTN3A1: A Legitimate Ménage à Trois in Dendritic Cells
ABCA1, apoA-I, and BTN3A1: A Legitimate Ménage à Trois in Dendritic Cells
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ABCA1、apoA-I 和 BTN3A1：树突状细胞中的合法家族
作者：
C. Riganti;B. Castella;M. Massaia
人Vγ 9VS 2 T细胞具有检测在特定情况下由哺乳动物细胞的甲羟戊酸（Mev）途径产生的超生理浓度的磷酸化抗原（pAg）的能力。异戊烯焦磷酸（IPP）是由Vγ 9VS 2 T细胞识别的原型pAg。B细胞衍生的肿瘤细胞（即，淋巴瘤和骨髓瘤细胞）和树突状细胞（DC）是Vγ 9VS 2 T细胞的优先靶标，因为它们产生显著量的IPP，其可以用唑来膦酸（ZA）加强。ZA是临床上可用于抑制破骨细胞活化的最有效的氨基二膦酸盐（NBP），也是Mev途径中法呢基焦磷酸合酶的非常有效的抑制剂。ZA处理的DC在上清液中产生并释放足以诱导Vγ 9VS 2 T细胞活化的皮摩尔IPP浓度。我们最近发现ATP结合盒转运蛋白A1（ABCA 1）在ZA处理的DC细胞外释放IPP中起主要作用。这种新型ABCA 1功能通过与IPP、载脂蛋白A-I（apoA-I）和亲酪蛋白-3A1（BTN 3A 1）的物理相互作用进行微调。可溶性IPP诱导Vγ 9VS 2 T细胞活化的机制仍有待阐明。可溶性IPP可能与旁观者细胞（如单核细胞、NK细胞、Vγ 9VS 2 T细胞或局部存在的任何其他细胞）的细胞表面上的BTN 3A 1、apoA-I或其他未知分子结合。研究这种情况可能代表进一步表征BTN 3A 1和其他分子在Vγ 9VS 2 T细胞识别可溶性IPP中的作用的独特机会。
Human Vγ9Vδ2 T cells have the capacity to detect supra-physiological concentrations of phosphoantigens (pAgs) generated by the mevalonate (Mev) pathway of mammalian cells under specific circumstances. Isopentenyl pyrophosphate (IPP) is the prototypic pAg recognized by Vγ9Vδ2 T cells. B-cell derived tumor cells (i.e., lymphoma and myeloma cells) and dendritic cells (DCs) are privileged targets of Vγ9Vδ2 T cells because they generate significant amounts of IPP which can be boosted with zoledronic acid (ZA). ZA is the most potent aminobisphosphonate (NBP) clinically available to inhibit osteoclast activation and a very potent inhibitor of farnesyl pyrophosphate synthase in the Mev pathway. ZA-treated DCs generate and release in the supernatants picomolar IPP concentrations which are sufficient to induce the activation of Vγ9Vδ2 T cells. We have recently shown that the ATP-binding cassette transporter A1 (ABCA1) plays a major role in the extracellular release of IPP from ZA-treated DCs. This novel ABCA1 function is fine-tuned by physical interactions with IPP, apolipoprotein A-I (apoA-I), and butyrophilin-3A1 (BTN3A1). The mechanisms by which soluble IPP induces Vγ9Vδ2 T-cell activation remain to be elucidated. It is possible that soluble IPP binds to BTN3A1, apoA-I, or other unknown molecules on the cell surface of bystander cells like monocytes, NK cells, Vγ9Vδ2 T cells, or any other cell locally present. Investigating this scenario may represent a unique opportunity to further characterize the role of BTN3A1 and other molecules in the recognition of soluble IPP by Vγ9Vδ2 T cells.
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影响因子：
11.2
作者：
Moriceau G;Ory B;Mitrofan L;Riganti C;Blanchard F;Brion R;Charrier C;Battaglia S;Pilet P;Denis MG;Shultz LD;Mönkkönen J;Rédini F;Heymann D
通讯作者：
Heymann D
影响因子：
8.8
作者：
Sebestyen Z;Scheper W;Vyborova A;Gu S;Rychnavska Z;Schiffler M;Cleven A;Chéneau C;van Noorden M;Peigné CM;Olive D;Lebbink RJ;Oostvogels R;Mutis T;Schuurhuis GJ;Adams EJ;Scotet E;Kuball J
通讯作者：
Kuball J
影响因子：
32.4
作者：
Sandstrom, Andrew;Peigne, Cassie-Marie;Leger, Alexandra;Crooks, James E.;Konczak, Fabienne;Gesnel, Marie-Claude;Breathnach, Richard;Bonneville, Marc;Scotet, Emmanuel;Adams, Erin J.
通讯作者：
Adams, Erin J.
DOI：
10.1016/j.bbrc.2015.06.150
发表时间：
2015-08-14
影响因子：
3.1
作者：
Manna, Pulak R.;Sennoune, Souad R.;Pruitt, Kevin
通讯作者：
Pruitt, Kevin