Department for Innovation in Biological, Agro-Food and Forest Systems, University of Tuscia, Largo dell'Università, Viterbo, Italy.
PLoS One. 2012;7(10):e47957. doi: 10.1371/journal.pone.0047957. Epub 2012 Oct 25.
Two lineages of T cells, expressing either the αβ T cell receptor (TR) or the γδ TR, exist in Gnathostomes. The latter type of T cells account for 1-10 % of T cells in blood and up to 30 % in the small intestine. They may recognize unconventional antigens (phosphorylated microbial metabolites, lipid antigens) without the need of major histocompatibility class I (MH1) or class II (MH2) presentation. In this work we have described cloning and structural characterization of TR -chain (TRG) from the teleost Dicentrarchus labrax. Further, by means of quantitative PCR analysis, we analyzed TRG expression levels both in poly I:C stimulated leukocytes in vitro, and following infection with betanodavirus in vivo. Two full length cDNAs relative to TRG, with the highest peptide and nucleotide identity with Japanese flounder, were identified. A multiple alignment analysis showed the conservation of peptides fundamental for TRG biological functions, and of the FGXG motif in the FR4 region, typical of most TR and immunoglobulin light chains. A 3D structure consisting of two domains mainly folded as beta strands with a sandwich architecture for each domain was also reported. TRG CDR3 of 8-18 AA in length and diversity in the TRG rearrangements expressed in thymus and intestine for a given V/C combination were evidenced by junction length spectratyping. TRG mRNA expression levels were high in basal conditions both in thymus and intestine, while in kidney and gut leukocytes they were up-regulated after in vitro stimulation by poly I:C. Finally, in juveniles the TRG expression levels were up-regulated in the head kidney and down-regulated in intestine after in vivo infection with betanodavirus. Overall, in this study the involvement of TRG-bearing T cells during viral stimulation was described for the first time, leading to new insights for the identification of T cell subsets in fish.
在有颌类脊椎动物中存在两种 T 细胞谱系,分别表达 αβ T 细胞受体 (TR) 或 γδ TR。后一种类型的 T 细胞占血液中 T 细胞的 1-10%,在小肠中占 30%。它们可以识别非常规抗原(磷酸化微生物代谢物、脂质抗原),而不需要主要组织相容性 I 类 (MH1) 或 II 类 (MH2) 呈递。在这项工作中,我们描述了来自鲈形目鱼牙鲆的 TR-链 (TRG) 的克隆和结构特征。此外,通过定量 PCR 分析,我们分析了聚肌苷酸:聚胞苷酸(poly I:C)刺激的体外白细胞以及体内感染神经坏死病毒(betanodavirus)后 TRG 的表达水平。鉴定了两个与 TRG 相对应的全长 cDNA,它们与日本牙鲆的肽和核苷酸同一性最高。多重比对分析显示,TRG 生物学功能的基本肽以及 FR4 区域的 FGXG 基序(大多数 TR 和免疫球蛋白轻链的典型特征)得到了保守。还报告了一个由两个主要折叠为β链的结构域组成的 3D 结构,每个结构域都具有三明治结构。通过连接长度谱分析,证明了 TRG 表达的 CDR3 长度为 8-18 个氨基酸,并且在胸腺和肠道中表达的 TRG 重排在给定的 V/C 组合中具有多样性。在基础条件下,TRG mRNA 在胸腺和肠道中的表达水平均较高,而在肾脏和肠道白细胞中,经 poly I:C 体外刺激后其表达水平上调。最后,在幼鱼中,感染神经坏死病毒后,头肾中的 TRG 表达水平上调,而肠道中的 TRG 表达水平下调。总的来说,在这项研究中,首次描述了 TRG 阳性 T 细胞在病毒刺激过程中的参与,为鱼类 T 细胞亚群的鉴定提供了新的见解。