MR1呈现与维生素B6相关的化合物,可由MR1反应性T细胞识别
Mitchell P McInerney1, Wael Awad1, Michael N T Souter2
1Department of Biochemistry and Molecular Biology and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
概括
主要的组织相容性复合体I类相关蛋白质 (MR1) 呈现维生素B6 (pyridoxal) 来激活T细胞,包括具有抗癌潜力的T细胞. 这一发现扩大了对MR1-受限T细胞激活的理解.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 代谢学 代谢学 代谢学
背景情况:
- 主体组织相容性复合体I类相关蛋白 (MR1) 呈现微生物代谢物以激活粘膜关联不变T细胞 (MAIT).
- MR1还向各种T细胞受体 (TCR) 呈现其他连接体,包括具有抗瘤活性的连接体,但这些连接体的全部范围尚不清楚.
研究的目的:
- 为了识别MR1呈现的新型连接体.
- 描述这些配体与MR1和MR1受限T细胞的相互作用.
- 探索MR1-配体相互作用在抗癌免疫中的潜力.
主要方法:
- 无偏的质谱测量以确定MR1结合的代谢物.
- 生物化学测试以评估MR1-配体结合和T细胞激活.
- 确定MR1-连接体复合物的晶体结构.
- 使用TCR转的细胞系进行T细胞激活检测.
主要成果:
- 皮里多克萨尔 (维生素B6) 和皮里多克萨尔-5酸盐被确定为自然存在的MR1配体.
- 皮里多和皮里多5-酸盐与MR1结合,包括依赖于Lys43.4的MR1*04等变体.
- 晶体结构揭示了pyridoxal和pyridoxal-5酸盐如何在MR1的A口袋内结合.
- 7.G5 TCR具有泛癌特异性,由MR1-呈现的氧化激活,由携带Arg9His多态的MR1全型增强识别.
结论:
- 皮里多克萨尔是一种天然存在的MR1配体.
- 呈现MR1的皮里多克萨尔激活T细胞,包括具有抗癌潜力的T细胞.
- 这一发现确立了维生素B6代谢,MR1和T细胞介导的抗瘤免疫之间的联系.
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