人与小鼠PD-1对比

IF 27.7 1区医学 Q1 IMMUNOLOGY

Nature Immunology Pub Date : 2025-01-31 DOI:10.1038/s41590-025-02086-x

Ioana Staicu

引用次数: 0

摘要

免疫检查点受体PD-1与其配体PD-L1的结合可触发磷酸酶SHP2的募集和激活，从而使T细胞受体（TCR）成分和共刺激信号通路去磷酸化。在Science Immunology中，Masubuchi等人发现小鼠PD-1的抑制功能比人类PD-1的抑制功能要低。在表达等量标记PD-1的人Jurkat T细胞、小鼠DO11.10 T细胞或原代人CD4+ T细胞中进行的滴定实验表明，在不同的TCR信号强度上，人PD-1 - pd - l1比小鼠PD-1 - pd - l1更能抑制IL-2的表达。与小鼠PD-1相比，人PD-1对PD-L1的亲和力高3.2倍，对PD-L2的亲和力高24倍，对SHP2的亲和力高2.9倍，并且在抗原提呈细胞(APC) -T细胞界面聚集更多。小鼠PD-1中较弱的SHP2结合主要是由于SHP2对接位点上游的Pro-Glu-Gln （PEQ）基序被His残基取代。转染了表达人源化细胞内结构域或His被人PEQ序列取代的小鼠PD-1的T细胞的黑素瘤接种小鼠，肿瘤生长更快，T细胞浸润更少，从而降低了Gzmb，增加了Tcf7的表达。因此，人PD-1比小鼠PD-1更有效地限制耗尽T细胞的增殖、效应功能和前体到终端的转化。原始参考文献：Sci。Immunol。https://doi.org/10.1126/sciimmunol.ads6295 (2025)

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Human versus mouse PD-1

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来源期刊

Nature Immunology 医学-免疫学

CiteScore

40.00

自引率

2.30%

发文量

248

审稿时长

4-8 weeks

期刊介绍： Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.