Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.
Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.
J Biol Chem. 2013 Sep 20;288(38):27519-27532. doi: 10.1074/jbc.M113.471045. Epub 2013 Aug 5.
The C-type lectin macrophage galactose-type lectin (MGL) exerts an immunosuppressive role reflected by its interaction with terminal GalNAc moieties, such as the Tn antigen, on CD45 of effector T cells, thereby down-regulating T cell receptor signaling, cytokine responses, and induction of T cell death. Here, we provide evidence for the pathways that control the specific expression of GalNAc moieties on human CD4(+) T cells. GalNAc epitopes were readily detectable on the cell surface after T cell activation and required de novo protein synthesis. Expression of GalNAc-containing MGL ligands was completely dependent on PKC and did not involve NF-κB. Instead, activation of the downstream ERK MAPK pathway led to decreased mRNA levels and activity of the core 1 β3GalT enzyme and its chaperone Cosmc, favoring the expression of Tn antigen. In conclusion, expression of GalNAc moieties mirrors the T cell activation status, and thus only highly stimulated T cells are prone to the suppressive action of MGL.
C 型凝集素巨噬细胞半乳糖凝集素（MGL）通过与其相互作用，对效应 T 细胞表面 CD45 上的末端 GalNAc 部分（如 Tn 抗原）发挥免疫抑制作用，从而下调 T 细胞受体信号、细胞因子反应和诱导 T 细胞死亡。在这里，我们提供了控制人类 CD4(+)T 细胞上特定 GalNAc 部分表达的途径的证据。T 细胞激活后，GalNAc 表位可在细胞表面上轻松检测到，且需要从头合成蛋白质。含 GalNAc 的 MGL 配体的表达完全依赖于 PKC，不涉及 NF-κB。相反，下游 ERK MAPK 途径的激活导致核心 1 β3GalT 酶及其伴侣 Cosmc 的 mRNA 水平和活性降低，有利于 Tn 抗原的表达。总之，GalNAc 部分的表达反映了 T 细胞激活状态，因此只有高度刺激的 T 细胞容易受到 MGL 的抑制作用。
