对瘤透淋巴细胞表达的孤儿T细胞受体的抗原鉴定
Marvin H Gee1, Arnold Han2, Shane M Lofgren3
1Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Departments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell
|December 26, 2017
概括
鉴定瘤抗原对于癌症免疫治疗至关重要. 这项研究揭示了瘤透淋巴细胞上的T细胞受体可以选,以找到它们的特定点,包括自我抗原,有助于癌症抗原的发现.
科学领域:
- 免疫学
- 癌症学
- 分子生物学
背景情况:
- 瘤透性淋巴细胞 (TILs) 在抗瘤免疫中起作用.
- TILs识别的特定抗原通常是未知的.
- 了解TIL抗原的特异性是开发癌症免疫疗法的关键.
研究的目的:
- 从人类结直肠癌TIL中识别T细胞受体 (TCR) 的抗原特异性.
- 探索用于TCR查的酵母显示-MHC库.
- 通过TILs发现新的瘤抗原.
主要方法:
- 用人白细胞抗原 (pHLA) 的酵母显示库进行查.
- 从结直肠腺癌的TIL中选由TCRs识别的抗原.
- 在不同的pHLA-A*02:01库中分析了TCR选择.
主要成果:
- 四个TIL衍生的TCR在pHLA库中显示出强烈的选择性.
- 三个TCR识别了非突变的自我抗原.
- 两种TCR识别出来自不同瘤的U2AF2相同的自我抗原.
- 证明TCR对它们的相关抗原具有高特异性.
结论:
- 对MHC结合的结构信息足以识别TCR标.
- 这种不偏的查方法有助于识别瘤抗原.
- 这些发现支持在癌症治疗中针对TILs识别的自我抗原的潜力.
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