Fish Health Research Section, Norwegian Veterinary Institute, Oslo, Norway.
Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Front Immunol. 2022 Jun 17;13:930312. doi: 10.3389/fimmu.2022.930312. eCollection 2022.
Protective cellular immune responses have been difficult to study in fish, due to lack of basic understanding of their T cell populations, and tools to study them. Cellular immunity is thus mostly ignored in vaccination and infection studies compared to humoral responses. High throughput sequencing, as well as access to well assembled genomes, now advances studies of cellular responses. Here we have used such resources to describe organization of T cell receptor beta genes in Atlantic salmon. Salmonids experienced a unique whole genome duplication approximately 94 million years ago, which provided these species with many functional duplicate genes, where some duplicates have evolved new functions or sub-functions of the original gene copy. This is also the case for T cell receptor beta, where Atlantic salmon has retained two paralogue T cell receptor beta regions on chromosomes 01 and 09. Compared to catfish and zebrafish, the genomic organization in both regions is unique, each chromosomal region organized with dual variable- diversity- joining- constant genes in a head to head orientation. Sequence identity of the chromosomal constant sequences between TRB01 and TRB09 is suggestive of rapid diversification, with only 67 percent as opposed to the average 82-90 percent for other duplicated genes. Using virus challenged samples we find both regions expressing bona fide functional T cell receptor beta molecules. Adding the 292 variable T cell receptor alpha genes to the 100 variable TRB genes from 14 subgroups, Atlantic salmon has one of the most diverse T cell receptor alpha beta repertoire of any vertebrate studied so far. Perhaps salmonid cellular immunity is more advanced than we have imagined.
由于对鱼类 T 细胞群体缺乏基本了解,也缺乏研究它们的工具,因此鱼类的细胞免疫在疫苗接种和感染研究中基本上被忽视,而与体液免疫相比。高通量测序以及对基因组的充分组装,现在推进了细胞反应的研究。在这里,我们利用这些资源描述了大西洋鲑鱼 T 细胞受体β基因的组织。鲑鱼经历了大约 9400 万年前的全基因组复制,这为这些物种提供了许多功能上的重复基因,其中一些重复基因进化出了原始基因拷贝的新功能或亚功能。T 细胞受体β也是如此,大西洋鲑鱼在染色体 01 和 09 上保留了两个同源的 T 细胞受体β区域。与鲶鱼和斑马鱼相比,这两个区域的基因组组织都是独特的,每个染色体区域都以头对头的方式组织成双变量-多样性-连接-恒定基因。TRB01 和 TRB09 之间染色体恒定序列的序列同一性表明快速多样化,只有 67%,而其他重复基因的平均比例为 82-90%。使用病毒挑战样本,我们发现这两个区域都表达了真正的功能性 T 细胞受体β分子。加上 14 个亚组的 292 个可变 T 细胞受体α基因和 100 个可变 TRB 基因,大西洋鲑鱼拥有迄今为止研究过的任何脊椎动物中最多样化的 T 细胞受体αβ库之一。也许鲑鱼的细胞免疫比我们想象的更先进。