抗原呈现分析显示了淋巴瘤免疫球蛋白新抗原的识别
Michael S Khodadoust1, Niclas Olsson2, Lisa E Wagar3
1Department of Medicine, Division of Oncology, Stanford University, Stanford, California 94305, USA.
Nature
|March 23, 2017
概括
研究人员在淋巴瘤瘤中发现了特定的新抗原,主要来自免疫球蛋白区域. 这些免疫球蛋白衍生新抗原可以被T细胞向有效的淋巴瘤免疫疗法.
科学领域:
- 免疫学
- 癌症学
- 基因组学
背景情况:
- 新抗原对于分辨癌细胞至关重要,并且可以作为免疫治疗的点.
- 在癌症研究中,个性化识别和验证新抗原是一个重大挑战.
研究的目的:
- 在人类地幔细胞淋巴瘤中发现和描述新抗原.
- 通过主要组织相容性复合物 (MHC) 分子研究新抗原的起源和表现.
- 评估免疫球蛋白衍生新抗原作为治疗点的潜力.
主要方法:
- 综合基因组和蛋白质组策略,以识别由MHC I类和II类分子呈现的瘤抗原.
- 来自17名地幔细胞淋巴瘤患者的MHC连体的系统性表征.
- 用于功能验证的外体序列和T细胞隔离.
主要成果:
- 所有鉴定到的新抗原都来自于淋巴瘤免疫球蛋白重链或轻链可变区域.
- 免疫球蛋白可变区域的体质突变主要是由MHCII类分子呈现的.
- 循环中针对免疫球蛋白衍生新抗原的CD4+ T细胞表现出杀死自身淋巴瘤细胞的能力.
结论:
- 结合MHC隔离,鉴定和外体序列的综合方法对发现瘤新抗原有效.
- 免疫球蛋白新抗原是上衣细胞淋巴瘤免疫治疗的重要点.
- 这一战略为开发个性化癌症疫苗和治疗提供了一个平台.
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