New regulation mechanism for CD8 T cell activation discovered by Xuetao Cao group
Source：CSI
2016-03-15
A great breakthrough and discovery about regulation mechanism of CD8 T cell activation was reported by professor Xuetao Cao colleague and had published in Nature Immunology journal in 2015.
CD8 T cell (cytotoxic T cell or killing cell) plays an important function in mediating host resistance to bacteria, virus infection and in eliciting antitumor activity. CD8 T cells can specifically kill target cells, such as tumor cells, pathogen infected or transplanted cells by granzymes and perforin; thereby eliminate infiltrating bacteria, viruses and tumor cells. However, hyperactivation of CD8 T cells can cause pathological immune responses, induce tissue damage, and result in autoimmune disease. As a result, the T cell signaling transduction mechanisms are very important in the process of T cell activation.
E3 ubiquitin ligase Nrdp1 was firstly cloned by Pro. Cao’s laboratory, and was named as Nrdp1 by other researchers. Previously researches (Pro. Cao laboratory) indicated the important roles of Nrdp1 in the regulation of innate immunity (Wang C, et al. Nat Immunol. 2009). Now the research team (from the China Academy of Chinese Medical Sciences, Second Military Medical University and Zhejiang University School of Medicine) found the new function of E3 ubiquitin ligase Nrdp1 in adaptive immunity.
Researches indicated that when CD8 T cells were activated, Nrdp1 could interact with Zap70, a key signaling molecular in T cell activation signaling transduction, and mediated the K33-linked polyubiquitination of zap70, and then the Sts1/2(suppressor of T cell receptor signaling) were recruited to Zap70 and bound to the ub-modified Zap70. After binding, Sts1/2 could dephosphate the phosphorylated and ubiquitinated Zap70 and inhibit the TCR signaling.
This article find a new function and mechanism of Nrdp1 in the regulation of CD8 T cell activation; Meanwhile this research may improve the negative regulation mechanism in TCR signaling pathway, and could provide insights for E3 ligase regulation in adaptive immune response. Furthermore, all studies about the roles and mechanisms of Nrdp1 in the regulation of CD8 T cells may provide new mechanistic explanations for adaptive immunity and autoimmune diseases regulated by E3 ubiquitin ligases, and bring a new potential target for the treatment of autoimmune diseases.
Paper: Yang M, Chen T, Li X, et al. K33-linked polyubiquitination of Zap70 by Nrdp1 controls CD8(+) T cell activation. Nat Immunol. 2015;16(12):1253-62.
CD8 T cell (cytotoxic T cell or killing cell) plays an important function in mediating host resistance to bacteria, virus infection and in eliciting antitumor activity. CD8 T cells can specifically kill target cells, such as tumor cells, pathogen infected or transplanted cells by granzymes and perforin; thereby eliminate infiltrating bacteria, viruses and tumor cells. However, hyperactivation of CD8 T cells can cause pathological immune responses, induce tissue damage, and result in autoimmune disease. As a result, the T cell signaling transduction mechanisms are very important in the process of T cell activation.
E3 ubiquitin ligase Nrdp1 was firstly cloned by Pro. Cao’s laboratory, and was named as Nrdp1 by other researchers. Previously researches (Pro. Cao laboratory) indicated the important roles of Nrdp1 in the regulation of innate immunity (Wang C, et al. Nat Immunol. 2009). Now the research team (from the China Academy of Chinese Medical Sciences, Second Military Medical University and Zhejiang University School of Medicine) found the new function of E3 ubiquitin ligase Nrdp1 in adaptive immunity.
Researches indicated that when CD8 T cells were activated, Nrdp1 could interact with Zap70, a key signaling molecular in T cell activation signaling transduction, and mediated the K33-linked polyubiquitination of zap70, and then the Sts1/2(suppressor of T cell receptor signaling) were recruited to Zap70 and bound to the ub-modified Zap70. After binding, Sts1/2 could dephosphate the phosphorylated and ubiquitinated Zap70 and inhibit the TCR signaling.
This article find a new function and mechanism of Nrdp1 in the regulation of CD8 T cell activation; Meanwhile this research may improve the negative regulation mechanism in TCR signaling pathway, and could provide insights for E3 ligase regulation in adaptive immune response. Furthermore, all studies about the roles and mechanisms of Nrdp1 in the regulation of CD8 T cells may provide new mechanistic explanations for adaptive immunity and autoimmune diseases regulated by E3 ubiquitin ligases, and bring a new potential target for the treatment of autoimmune diseases.
Paper: Yang M, Chen T, Li X, et al. K33-linked polyubiquitination of Zap70 by Nrdp1 controls CD8(+) T cell activation. Nat Immunol. 2015;16(12):1253-62.
