Vγ9 and Vδ2 T cell antigen receptor genes and butyrophilin 3 (BTN3) emerged with placental mammals and are concomitantly preserved in selected species like alpaca (Vicugna pacos)
Vγ9 and Vδ2 T cell antigen receptor genes and butyrophilin 3 (BTN3) emerged with placental mammals and are concomitantly preserved in selected species like alpaca (Vicugna pacos)
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DOI：
10.1007/s00251-014-0763-8
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发表时间：
2014-04-01
期刊：
影响因子：
3.2
通讯作者：
Herrmann, Thomas
中科院分区：
文献类型：
--
作者：
Karunakaran, Mohindar M.;Goebel, Thomas W.;Herrmann, Thomas
人 V γ 9V δ 2 T 细胞识别类异戊二烯代谢的磷酸化产物（磷酸抗原）PAg，TCR 包含依赖于抗原呈递细胞表达的嗜丁酸蛋白 3 (BTN3) 的 V γ 9JP γ 链和 V δ 2 δ 链。它们在许多感染中被大量激活并表现出抗肿瘤活性，到目前为止，它们被认为只存在于高等灵长类动物中。我们对数据库进行了全面分析，并在两种胎盘巨目动物物种中鉴定出了这三个基因，但在啮齿类动物中却没有。计算机可翻译的 V gamma 9、V delta 2 和 BTN3 基因的常见出现或丢失表明它们基于功能关系的共同进化。在羊驼 (Vicugna pacos) 的外周淋巴细胞中，发现了特征性的 V gamma 9JP 重排和框内 V delta 2 重排，并且可以在 TCR 阴性小鼠 T 细胞杂交瘤中共表达，从而挽救 CD3 的表达和功能。最后，羊驼 BTN3 胞外域的数据库序列分析揭示了人 BTN3A1 的 PAg 结合残基的完全保守性。总之，我们在胎盘哺乳动物中展示了 V gamma 9 和 V delta 2 TCR 基因以及假定的抗原呈递分子 BTN3 的基因的出现和保存，并为分析羊驼作为第一个拥有 V gamma 9V delta 2 T 细胞的非灵长类物种的候选物种奠定了基础。
Human V gamma 9V delta 2 T cells recognize phosphorylated products of isoprenoid metabolism (phosphoantigens) PAg with TCR comprising V gamma 9JP gamma-chains and V delta 2 delta-chains dependent on butyrophilin 3 (BTN3) expressed by antigen-presenting cells. They are massively activated in many infections and show anti-tumor activity and so far, they have been considered to exist only in higher primates. We performed a comprehensive analysis of databases and identified the three genes in species of both placental magnorders, but not in rodents. The common occurrence or loss of in silico translatable V gamma 9, V delta 2, and BTN3 genes suggested their co-evolution based on a functional relationship. In the peripheral lymphocytes of alpaca (Vicugna pacos), characteristic V gamma 9JP rearrangements and in-frame V delta 2 rearrangements were found and could be co-expressed in a TCR-negative mouse T cell hybridoma where they rescued CD3 expression and function. Finally, database sequence analysis of the extracellular domain of alpaca BTN3 revealed complete conservation of proposed PAg binding residues of human BTN3A1. In summary, we show emergence and preservation of V gamma 9 and V delta 2 TCR genes with the gene of the putative antigen-presenting molecule BTN3 in placental mammals and lay the ground for analysis of alpaca as candidate for a first non-primate species to possess V gamma 9V delta 2 T cells.