PD-L2 is a second ligand for PD-I and inhibits T cell activation
PD-L2 is a second ligand for PD-I and inhibits T cell activation
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DOI：
10.1038/85330
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发表时间：
2001-03-01
影响因子：
30.5
通讯作者：
Freeman, GJ
中科院分区：
文献类型：
--
作者：
Latchman, Y;Wood, CR;Freeman, GJ
程序性死亡受体1（PD - 1）缺陷型小鼠会患上多种自身免疫性疾病，这表明这种免疫抑制性受体在免疫耐受中起着重要作用。在此我们鉴定出PD - 1配体2（PD - L2）是PD - 1的第二种配体，并比较了PD - L1和PD - L2的功能及表达。PD - L2与PD - 1结合会显著抑制CD4⁺ T细胞中T细胞受体（TCR）介导的增殖以及细胞因子的产生。在低抗原浓度下，PD - L2 - PD - 1相互作用会抑制强烈的B7 - CD28信号；相反，在高抗原浓度下，PD - L2 - PD - 1相互作用会减少细胞因子的产生，但不抑制T细胞增殖。PD - L - PD - 1相互作用导致细胞周期停滞在G₀/G₁期，但不会增加细胞死亡。此外，与单独的TCR结合相比，PD - 1 + TCR的连接会导致SHP - 2的快速磷酸化。通过干扰素γ处理，抗原呈递细胞上的PD - L表达上调，并且在一些正常组织和肿瘤细胞系中也存在。综上所述，这些研究表明PD - L1和PD - L2的功能存在重叠，并指出PD - L - PD - 1通路在调节T细胞应答中起着关键作用。
Programmed death I (PD-1)-deficient mice develop a variety of autoimmune-like diseases, which suggests that this immunoinhibitory receptor plays an important role in tolerance. We identify here PD-1 ligand 2 (PD-L2) as a second ligand for PD-1 and compare the function and expression of PD-L1 and PD-L2. Engagement of PD-1 by PD-L2 dramatically inhibits T cell receptor (TCR)-mediated proliferation and cytokine production by CD4(+) T cells,At low antigen concentrations, PD-L2-PD-1 interactions inhibit strong B7-CD28 signals, In contrast, at high antigen concentrations, PD-L2-PD-1 interactions reduce cytokine production but do not inhibit T cell proliferation. PD-L-PD-1 interactions lead to cell cycle arrest in G(0)/G(1) but do not increase cell death. In addition, ligation of PD-1 + TCR leads to rapid phosphorylation of SHP-2, as compared to TCR ligation alone, PD-L expression was up-regulated on antigen-presenting cells by interferon gamma treatment and was also present on some normal tissues and tumor cell lines,Taken together, these studies show overlapping functions of PD-L1 and PD-L2 and indicate a key role for the PD-L-PD-1 pathway in regulating T cell responses.