一个自然选择的αβ-T细胞受体结合HLA-DQ2分子,而不会与呈现的一起接触
Jia Jia Lim1, Claerwen M Jones1, Tiing Jen Loh1
1Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Nature communications
|April 8, 2025
概括
研究人员发现了一种独特的T细胞受体 (TCR),可以识别HLA-DQ2.5分子而不与特定结合,从而挑战免疫学中的共同识别范式.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 分子识别分子识别
背景情况:
- T细胞受体 (TCRs) 通常识别由主要基因相容性复合体 (MHC) 分子呈现的抗原.
- 现有的结构数据显示TCR--MHC对接的变化,但坚持共同识别原则.
研究的目的:
- 为了识别和描述一个新型的TCR,它偏离了既定的TCR--MHC共同识别范式.
- 阐明TCR与MHC分子的异性结合的结构基础.
主要方法:
- 使用HLA-DQ2.5-四聚体来识别人类外周血液中的特定TCR (G9).
- 确定TCR-HLA-DQ2.5-复合物的晶体结构.
- 对HLA类I和II分子进行了高通量选,以检测G9 TCR活性.
主要成果:
- 鉴定了一种TRAV12-1+-TRBV5-1+ G9 TCR,可以独立于结合HLA-DQ2.5.
- 结构分析显示了一个反向对接拓,G9 TCR与HLA-DQ2.5的β1区域接触,距离结裂.
- G9 TCR显示了全HLA-DQ2反应性,HLA-DQ2.5的Leu-55对特异性至关重要,并阻止了CD4结合,从而抑制了T细胞激活.
结论:
- 描述了一种自然选择的αβTCR,它打破了传统的TCR--MHC联合识别模型.
- G9 TCR对HLA-DQ2.5的异性结合为T细胞受体特异性和免疫识别机制提供了新的见解.
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