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多态KIR3DL3表达调节组织居民和先天性T细胞

William H Palmer^1,2, Laura Ann Leaton^1,2, Ana Campos Codo^1,2

¹Department of Biomedical Informatics, University of Colorado School of Medicine, Aurora, CO, USA.

Science immunology

|June 30, 2023

概括

杀伤细胞免疫球蛋白样受体3DL3 (KIR3DL3) 主要存在于T细胞,而不是NK细胞中,并且可以抑制T细胞功能. KIR3DL3的表达有所变化,影响免疫检查点疗法.

科学领域:

免疫学免疫学免疫学
细胞生物学细胞生物学
分子生物学分子生物学

背景情况:

杀手细胞免疫球蛋白类受体 (KIR) 通常在自然杀手 (NK) 细胞上起作用,识别HLA类I联体.
作为一种抑制性KIR,KIR3DL3结合了B7家族联体HHLA2,是免疫检查点抑制的目标.
然而,KIR3DL3的表达和功能在很大程度上仍然没有被描述.

研究的目的:

为了研究KIR3DL3.3的表达特征和生物功能.
为了确定KIR3DL3表达细胞的细胞分布和特征.
探索KIR3DL3表达及其变体对免疫检查点向的影响.

主要方法:

进行了广泛的转录组分析,以确定KIR3DL3表达.
高分辨率的流细胞计和单细胞转录组学用于表征KIR3DL3+ T细胞.
分析T细胞受体 (TCR) 使用情况和功能测定,包括KIR3DL3结合.

主要成果:

在 γδ 和 CD8+ T 细胞中,而不是 NK 细胞中,KIR3DL3 的表达很高,在肺和消化道中具有丰富的存在.
KIR3DL3+ T细胞表现出激活的过渡性记忆表型和功能减少.
通过KIR3DL3结合,TCR介导的T细胞刺激可以被抑制,并且某些遗传变异会影响KIR3DL3表达水平.

结论:

在非传统的T细胞激活过程中,KIR3DL3被上调,其表达在个体之间是可变的.
研究结果表明KIR3DL3在T细胞调节中发挥作用,并对个性化KIR3DL3/HHLA2免疫检查点抑制策略产生影响.

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