Individual Vγ2-Jγ1.2+ T cells respond to both isopentenyl pyrophosphate and Daudi cell stimulation:: generating tumor effectors with low molecular weight phosphoantigens

Individual Vγ2-Jγ1.2+ T cells respond to both isopentenyl pyrophosphate and Daudi cell stimulation:: generating tumor effectors with low molecular weight phosphoantigens
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DOI:
10.1007/s00262-006-0235-6
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发表时间:
2007-06-01
影响因子:
5.8
通讯作者:
Pauza, C. David
Pauza, C. David
中科院分区:
医学3区
文献类型:
--
作者:
Hebbeler, Andrew M.;Cairo, Cristiana;Pauza, C. David

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人V γ 2V δ 2 T细胞表现出T细胞受体依赖性、MHC非限制性的抗原识别,并在肿瘤和病原体免疫中发挥重要作用。为了表征V γ 2V δ 2 TCR的抗原识别,我们使用了光谱分析和CDR 3序列分析的组合方法,该方法测量了用磷酸化抗原(异戊烯焦磷酸)或辐照的肿瘤细胞系(Daudi B淋巴瘤)刺激前后TCR库的变化。在这里,我们描述了共同的V γ 2链,基本上参与了磷抗原和肿瘤细胞的反应。常见V γ 2链的识别特性解释了通过磷酸化抗原刺激扩增的V γ 2V δ 2 T细胞特异性识别并杀死一些但不是所有肿瘤细胞系的观察结果。我们的研究进一步证明了通过给予低分子量磷抗原和增强循环V γ 2V δ 2 T细胞的频率和肿瘤效应功能来刺激肿瘤免疫的努力。
Human V gamma 2V delta 2 T cells exhibit T cell receptor-dependent, MHC-unrestricted recognition of antigen and play important roles in tumor and pathogen immunity. To characterize antigen recognition by the V gamma 2V delta 2 TCR, we used the combined approach of spectratyping and CDR3 sequence analysis that measures changes in the TCR repertoire before and after stimulation with a phosphoantigen (isopentenyl pyrophosphate) or an irradiated tumor cell line (Daudi B lymphoma). Here we describe common V gamma 2 chains that are substantially involved in the response to both phosphoantigens and tumor cells. The recognition properties of common V gamma 2 chains explains the observation that V gamma 2V delta 2 T cells expanded by phosphoantigen stimulation specifically recognize and kill some but not all tumor cell lines. Our studies further justify efforts to stimulate tumor immunity by administering low molecular weight phosphoantigens and boosting the frequency and tumor effector functions of circulating V gamma 2V delta 2 T cells.