The evolution of vertebrate antigen receptors: a phylogenetic approach.
The evolution of vertebrate antigen receptors: a phylogenetic approach.
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DOI：
10.1093/oxfordjournals.molbev.a026227
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发表时间：
2000
影响因子：
10.7
通讯作者：
M. Richards;J. Nelson
中科院分区：
文献类型：
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作者：
M. Richards;J. Nelson
具有α-βT细胞受体(TCR)的经典T细胞是脊椎动物自我-非我免疫识别的主导范式的重要组成部分。当α-βT细胞与抗原呈递细胞表面的MHC分子结合时，它们就能识别外来的多肽抗原。Gamma Delta T细胞具有类似的受体，通常认为这些T细胞还需要特殊的抗原递呈分子来进行免疫识别，我们称之为“间接抗原识别”。B细胞受体或免疫球蛋白直接与抗原结合，而不需要特殊的抗原呈递分子的帮助。在系统发生学上，人们假设T细胞受体和编码它们的基因是一个单系群，在分裂成两种TCR之前，“间接”抗原识别进化成了两种类型的TCR。然而，最近有人提出，与免疫球蛋白(Ig)一样，Gamma-Delta-TCR与抗原直接结合。这对间接抗原识别是TCR的共同特征的零假设以及所有TCR基因序列形成单系群的假设提出了质疑。为了确定是否有可能对TCR基因之间的抗原识别和其他历史关系做出替代解释，我们对编码TCR和Ig分子基本亚基的恒定区和可变区的氨基酸序列进行了系统发育分析。我们使用了最大简约法和基于遗传距离的方法，都没有找到对TCR单调性假说的有力支持。对恒定区的分析表明，TCR伽马或增量序列是最古老的，这意味着祖先的免疫细胞就像现代的伽马三角洲T细胞。从这个类伽马三角洲的祖先产生了α-βT细胞和B细胞，这意味着间接抗原识别确实是α-β-TCR的一种派生特性。由于对抗原结合序列的强烈选择，可变区的分析变得复杂，但暗示直接抗原结合是祖先的条件。
Classical T cells, those with alpha beta T-cell receptors (TCRs), are an important component of the dominant paradigm for self-nonself immune recognition in vertebrates. alpha beta T cells recognize foreign peptide antigens when they are bound to MHC molecules on the surfaces of antigen-presenting cells. gamma delta T cells bear a similar receptor, and it is often assumed that these T cells also require specialized antigen-presenting molecules for immune recognition, which we term "indirect antigen recognition." B-cell receptors, or immunoglobulins, bind directly to antigens without the help of a specialized antigen-presenting molecule. Phylogenetically, it has been assumed that T-cell receptors and the genes that encode them are a monophyletic group, and that "indirect" antigen recognition evolved before the split into two types of TCR. Recently, however, it has been proposed that gamma delta-TCRs bind directly to antigens, as do immunoglobulins (Ig's). This calls into question the null hypothesis that indirect antigen recognition is a common characteristic of TCRs and, by extension, the hypothesis that all TCR gene sequences form a monophyletic group. To determine whether alternative explanations for antigen recognition and other historical relationships among TCR genes might be possible, we performed phylogenetic analyses on amino acid sequences of the constant and variable regions which encode the basic subunits of TCR and Ig molecules. We used both maximum-parsimony and genetic distance-based methods and could find no strong support for the hypothesis of TCR monophyly. Analyses of the constant region suggest that TCR gamma or delta sequences are the most ancient, implying that the ancestral immune cell was like a modern gamma delta T cell. From this gamma delta-like ancestor arose alpha beta T cells and B cells, implying that indirect antigen recognition is indeed a derived property of alpha beta-TCRs. Analyses of the variable regions are complicated by strong selection on antigen-binding sequences, but imply that direct antigen binding is the ancestral condition.