Bw4配体和直接结合T细胞受体诱导了HLA A和B等位基因的选择
Reut Levi1, Lee Levi1, Yoram Louzoun1
1Department of Mathematics, Bar-Ilan University, Ramat Gan, Israel.
Frontiers in immunology
|December 11, 2023
概括
人类白细胞抗原 (HLA) 的等位基因频率现在可以从它们的序列中预测,揭示选择压力. 最强的选择影响杀手细胞免疫球蛋白样受体 (KIR) 和T细胞受体 (TCR) 结合区域,而不仅仅是呈现.
科学领域:
- 免疫遗传学 免疫遗传学
- 人口遗传学 人口遗传学
- 计算生物学 计算生物学
背景情况:
- 人类白细胞抗原 (HLA) 区域对免疫反应至关重要,表现出可能由病原体多样性驱动的平衡选择.
- 在HLA等位基因上的选择影响着种群遗传学,在呈现病毒表位和与T细胞受体 (TCR) 和杀手细胞免疫球蛋白类受体 (KIR) 相互作用方面发挥作用.
研究的目的:
- 开发和应用一种机器学习方法,从它们的序列中预测HLA等位基因频率.
- 根据预测的频率量化作用于HLA等位基的选择压力.
主要方法:
- 来自600多万血造干细胞 (HSC) 捐赠者的综合HLA等位基频率数据.
- 利用一种新的机器学习方法,从序列数据中预测HLA等位基因频率.
主要成果:
- 首次从它们的序列直接预测HLA等位基频率的能力.
- 确定了对KIR结合区域起作用的最强的选择,其次是结合裂.
- 发现KIR和TCR相互作用的选择集中在带正电荷的残留物 (例如,氨酸),而一些结裂位置 (例如,氨酸) 与等位基频率没有关联.
结论:
- 预测HLA等位基因频率提供了对选择的定量衡量.
- 在HLA中平衡选择不仅涉及呈现,还涉及KIR和TCR结合相互作用的积极选择.
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