Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Clin Immunol. 2019 Jul;204:50-56. doi: 10.1016/j.clim.2018.10.009. Epub 2018 Oct 19.
Signaling Lymphocyte Activation Molecule (SLAM) family receptors are expressed on different types of hematopoietic cells and play important role in immune regulation in health and disease. 2B4 (CD244, SLAMF4) and CS1 (CD319, CRACC, SLAMF7) were originally identified as NK cell receptors regulating NK cell cytolytic activity. 2B4 is expressed on all NK cells, a subpopulation of T cells, monocytes and basophils. Unlike other activating and inhibitory receptors, 2B4 (CD244) interaction with its ligand CD48 has been shown to mediate both activating and inhibitory functions. Defective signaling via 2B4 due to mutations in signaling adaptor SAP contributes to X-linked lymphoproliferative Disease (XLP). Expression of 2B4 and CS1 are altered in systemic lupus erythematosus (SLE). CS1 is overexpressed in multiple myeloma (MM) and anti-CS1 mab (Elotuzumab/Empliciti) has been approved by FDA as a breakthrough drug for treatment for MM patients. CAR -T cells or CAR- NK cells containing full length CS1 or the signaling domain of 2B4 with TCR-ζ have shown promising results to treat cancer and autoimmune diseases.
信号淋巴细胞激活分子（SLAM）家族受体表达于不同类型的造血细胞上，在健康和疾病状态下的免疫调节中发挥重要作用。2B4（CD244、SLAMF4）和 CS1（CD319、CRACC、SLAMF7）最初被鉴定为调节 NK 细胞细胞毒性的 NK 细胞受体。2B4 表达于所有 NK 细胞、部分 T 细胞、单核细胞和嗜碱性粒细胞上。与其他激活和抑制性受体不同，2B4（CD244）与其配体 CD48 的相互作用已被证明具有激活和抑制双重功能。由于信号衔接蛋白 SAP 中的突变导致 2B4 信号转导缺陷，引起 X 连锁淋巴组织增生性疾病（XLP）。2B4 和 CS1 的表达在系统性红斑狼疮（SLE）中发生改变。CS1 在多发性骨髓瘤（MM）中过表达，抗 CS1 mAb（Elotuzumab/Empliciti）已被 FDA 批准为 MM 患者治疗的突破性药物。含有全长 CS1 或 2B4 信号结构域与 TCR-ζ 的 CAR-T 细胞或 CAR-NK 细胞在治疗癌症和自身免疫性疾病方面显示出良好的效果。
