澳大利亚墨尔本大学Adam P. Uldrich、Dale I. Godfrey以及乐卓博大学Andreas Behren等研究人员合作发现，嗜乳脂蛋白2A1对γδT细胞的磷抗原反应至关重要。相关论文2020年1月9日在线发表在《科学》上。

研究人员表示，γδT细胞对保护性免疫至关重要。在人类中，大多数γδT细胞表达Vγ9Vδ2⁺T细胞受体（TCR），这些受体对细胞病原体产生的、癌症过度表达的磷抗原（pAg）有反应。但是，由这些γδTCR识别的分子靶标是未知的。

研究人员鉴定出嗜乳脂蛋白2A1（BTN2A1）是与Vγ9⁺TCRγ链结合的关键配体。BTN2A1与另一种嗜乳脂蛋白BTN3A1结合，后者共同作用以启动对pAg的反应。此外，还需要第二种配体（可能是BTN3A1）与包含Vδ2的单独TCR域结合。这种依赖于Ag的T细胞活化独特模式提高了人们对pAg识别疾病的理解，并为基于γδT细胞的免疫疗法发展创造了机会。

附：英文原文

Title: Butyrophilin 2A1 is essential for phosphoantigen reactivity by γδ T cells

Author: Marc Rigau, Simone Ostrouska, Thomas S. Fulford, Darryl N. Johnson, Katherine Woods, Zheng Ruan, Hamish E.G. McWilliam, Christopher Hudson, Candani Tutuka, Adam K. Wheatley, Stephen J. Kent, Jose A. Villadangos, Bhupinder Pal, Christian Kurts, Jason Simmonds, Matthias Pelzing, Andrew D. Nash, Andrew Hammet, Anne M. Verhagen, Gino Vairo, Eugene Maraskovsky, Con Panousis, Nicholas A. Gherardin, Jonathan Cebon, Dale I. Godfrey, Andreas Behren, Adam P. Uldrich

Issue&Volume: 2020/01/09

Abstract: Gamma delta (γδ) T cells are essential to protective immunity. In humans, most γδ T cells express Vγ9Vδ2+ T cell receptors (TCRs) that respond to phosphoantigens (pAg) produced by cellular pathogens and overexpressed by cancers. However, the molecular targets recognized by these γδTCRs are unknown. Here, we identify butyrophilin 2A1 (BTN2A1) as a key ligand that binds to the Vγ9+ TCR γ-chain. BTN2A1 associates with another butyrophilin, BTN3A1, which act together to initiate responses to pAg. Furthermore, binding of a second ligand, possibly BTN3A1, to a separate TCR domain incorporating Vδ2 is also required. This unique mode of Ag-dependent T cell activation advances our understanding of diseases involving pAg recognition and creates opportunities for the development of γδ T cell-based immunotherapies.

DOI: 10.1126/science.aay5516

Source: https://science.sciencemag.org/content/early/2020/01/08/science.aay5516