Up-regulation of cytolytic functions of human Vδ2- γδ T lymphocytes through engagement of ILT2 expressed by tumor target cells
Up-regulation of cytolytic functions of human Vδ2- γδ T lymphocytes through engagement of ILT2 expressed by tumor target cells
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DOI：
10.1182/blood-2010-09-309781
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发表时间：
2011-03-10
期刊：
影响因子：
20.3
通讯作者：
Scotet, Emmanuel
中科院分区：
文献类型：
--
作者：
Harly, Christelle;Peyrat, Marie-Alix;Scotet, Emmanuel
在人类中，大多数外周血γ δ T细胞表达V γ γ 9V δ 2 T细胞受体（TCR）并识别非肽磷酸化抗原。相反，大多数组织源性γ δ T细胞，主要位于脾脏和上皮，优先使用V δ 1或V δ 3链与不同的V γ链配对形成TCR。我们对人类V δ 2(-) γ δ T细胞的抗原特异性和共刺激需求的了解仍然有限。为了解决这一重要问题，我们鉴定了一种单克隆抗体（mAb 256）的特异性，筛选了其特异性抑制几种人V δ 2(-) γ δ t细胞克隆对转化B细胞的细胞溶解反应的能力。我们发现mAb 256不靶向TCR配体，但阻断效应γ δ T细胞上的非TCR分子与肿瘤靶标表达的ILT2分子之间的关键相互作用。与先前报道的NK受体对经典和非经典主要组织相容性复合体（MHC） I类分子的特异性一致，使用MHC I类或ILT2特异性单克隆抗体和ILT2- fc分子阻断MHC I类/ILT2相互作用可抑制肿瘤诱导的V γ 8V δ 3 t细胞克隆的激活。因此，本研究描述了一种新的细胞毒性T淋巴细胞激活途径，涉及MHC I类参与γ δ T细胞。[血液杂志];2011;117(10):2864-2873]
In humans, the majority of peripheral blood gamma delta T cells expresses V gamma 9V delta 2 T-cell receptors (TCR) and recognize nonpeptidic phosphorylated antigens. In contrast, most tissue-derived gamma delta T cells, which are located mainly in spleen and epithelia, preferentially use V delta 1 or V delta 3 chains paired with diverse V gamma chains to form their TCR. Our knowledge about the antigenic specificity and costimulation requirements of human V delta 2(-) gamma delta T cells remains limited. In an attempt to address this important issue, we characterized the specificity of a monoclonal antibody (mAb 256), screened for its ability to specifically inhibit cytolytic responses of several human V delta 2(-) gamma delta T-cell clones against transformed B cells. We show that mAb 256 does not target a TCR ligand but blocks key interactions between non-TCR molecules on effector gamma delta T cells and ILT2 molecule, expressed by tumor targets. In line with the previously reported specificity of this NK receptor for classic and nonclassic major histocompatibility complex (MHC) class I molecules, blockade of MHC class I/ILT2 interactions using MHC class I- or ILT2-specific mAbs and ILT2-Fc molecules inhibited tumor-induced activation of V gamma 8V delta 3 T-cell clones. Therefore, this study describes a new cytotoxic T lymphocyte activation pathway involving MHC class I engagement on gamma delta T cells. (Blood. 2011; 117(10): 2864-2873)