Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, NSW, Australia.
Immunobiology. 2013 Feb;218(2):213-24. doi: 10.1016/j.imbio.2012.04.003. Epub 2012 May 1.
Semi-invariant T cell receptors (TCRs) found on natural killer T (NKT) and mucosal-associated invariant T (MAIT) cells are characterized by the use of invariant variable (V) and joining (J) gene combinations in the TCR α-chain, as well as ubiquitous canonical TCRα amino acid sequences that are dominant in many individuals and similar across species. That they are so prevalent indicates that they occupy an important niche within the immune system. However, these TCRs are produced by a largely random gene recombination process, which seems a risky approach for the immune system to acquire these innate-like cells. We surveyed studies reporting NKT and MAIT TCRα sequences for six and four different species, respectively. Although the germline nature of the canonical human and mouse NKT and mouse MAIT TCRα sequences and an overlap of nucleotides between the mouse MAIT-related Vα and Jα genes have been noted in previous studies, in this study we demonstrate that, for all reported species, the canonical TCRα amino acid sequences can be encoded by at least one germline-derived nucleotide sequence. Moreover, these nucleotide sequences can utilize an overlap between the Vα and Jα genes in their production, which enables them to be produced by a large variety of recombination mechanisms. We investigated the role of these TCRα features in the production of the canonical NKT and MAIT TCRα sequences. In computer simulations of a random recombination process involving the invariant NKT and MAIT TCRα gene combinations for each species, the canonical NKT and MAIT TCRα sequences were the first or second most generated of all sequences with the CDR3α length restrictions associated with NKT and MAIT cells. These results suggest that the immune machinery enables the canonical NKT and MAIT TCRα sequences to be produced with great efficiency through the process of convergent recombination, ensuring their prevalence across individuals and species.
天然杀伤 T（NKT）细胞和黏膜相关不变 T（MAIT）细胞上发现的半不变 T 细胞受体（TCR）的特征是 TCRα 链中使用不变可变（V）和连接（J）基因组合，以及在许多个体中占优势且在物种间相似的普遍规范 TCRα 氨基酸序列。它们如此普遍存在表明它们在免疫系统中占据重要位置。然而，这些 TCR 是通过一个很大程度上随机的基因重组过程产生的，这对免疫系统来说似乎是一种冒险的方法，因为它需要获得这些先天样细胞。我们调查了分别报告六个和四个不同物种的 NKT 和 MAIT TCRα 序列的研究。尽管以前的研究已经注意到规范的人类和小鼠 NKT 和小鼠 MAIT TCRα 序列的种系性质以及小鼠 MAIT 相关 Vα 和 Jα 基因之间的核苷酸重叠，但在本研究中，我们证明对于所有报告的物种，规范的 TCRα 氨基酸序列可以由至少一个种系衍生的核苷酸序列编码。此外，这些核苷酸序列可以在其产生过程中利用 Vα 和 Jα 基因之间的重叠，从而使它们能够通过多种重组机制产生。我们研究了这些 TCRα 特征在产生规范的 NKT 和 MAIT TCRα 序列中的作用。在涉及每个物种的不变 NKT 和 MAIT TCRα 基因组合的随机重组过程的计算机模拟中，具有与 NKT 和 MAIT 细胞相关的 CDR3α 长度限制的规范 NKT 和 MAIT TCRα 序列是所有序列中首先或第二最常产生的序列。这些结果表明，免疫机制通过收敛性重组过程使规范的 NKT 和 MAIT TCRα 序列得以高效产生，确保它们在个体和物种中广泛存在。
