Extensive T-Cell Epitope Repertoire Sharing among Human Proteome, Gastrointestinal Microbiome, and Pathogenic Bacteria: Implications for the Definition of Self.
Extensive T-Cell Epitope Repertoire Sharing among Human Proteome, Gastrointestinal Microbiome, and Pathogenic Bacteria: Implications for the Definition of Self.
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DOI：
10.3389/fimmu.2015.00538
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发表时间：
2015
影响因子：
7.3
通讯作者：
Homan EJ
中科院分区：
文献类型：
--
作者：
Bremel RD;Homan EJ
t细胞受体与mhc结合肽的结合在自我和非自我区分中起着关键作用。只有mhc结合肽中氨基酸的一个子集，通常是五聚体，形成暴露于t细胞受体的基序。我们对两组细菌（包括病原体和胃肠道微生物组）的总蛋白质组中暴露的t细胞氨基酸基序库与人类蛋白质组和免疫球蛋白进行了分类和比较。考虑到结合t细胞受体的基序最多有205个或320万个，基序的使用有相当大的重叠。我们发现，不含免疫球蛋白的人类蛋白质组只包含四分之三可能的基序，其中65.3%也存在于两种复合细菌蛋白质组中。很少有基序是人类蛋白质组所特有的。免疫球蛋白可变区携带多种多样的t细胞暴露基序（TCEMs），提供了病原体、微生物组和人类蛋白质组中发现的基序的分层随机样本。单个细菌属和种所携带的免疫球蛋白和人类蛋白质组匹配基序的含量各不相同。分枝杆菌和伯克霍尔德氏杆菌携带这种匹配基序的含量特别高。一些细菌保留了与人类蛋白质组独特的基序特征和基序共享模式。这意味着，区分自我与非自我并不取决于个体的TCEM，而是取决于信号的复杂和动态叠加，其中相同的TCEM可能在不同的生物体中发挥不同的作用，特定TCEM出现的频率影响其效果。观察到的模式为细菌免疫逃避和干预策略提供了线索，包括疫苗设计。免疫球蛋白衍生肽的宽度和不同的频率模式表明免疫球蛋白在维持广泛反应的t细胞库中的作用。
T-cell receptor binding to MHC-bound peptides plays a key role in discrimination between self and non-self. Only a subset, typically a pentamer, of amino acids in a MHC-bound peptide form the motif exposed to the T-cell receptor. We categorize and compare the T-cell exposed amino acid motif repertoire of the total proteomes of two groups of bacteria, comprising pathogens and gastrointestinal microbiome organisms, with the human proteome and immunoglobulins. Given the maximum 205, or 3.2 million of such motifs that bind T-cell receptors, there is considerable overlap in motif usage. We show that the human proteome, exclusive of immunoglobulins, only comprises three quarters of the possible motifs, of which 65.3% are also present in both composite bacterial proteomes. Very few motifs are unique to the human proteome. Immunoglobulin variable regions carry a broad diversity of T-cell exposed motifs (TCEMs) that provides a stratified random sample of the motifs found in pathogens, microbiome, and the human proteome. Individual bacterial genera and species vary in the content of immunoglobulin and human proteome matched motifs that they carry. Mycobacteria and Burkholderia spp carry a particularly high content of such matched motifs. Some bacteria retain a unique motif signature and motif sharing pattern with the human proteome. The implication is that distinguishing self from non-self does not depend on individual TCEMs, but on a complex and dynamic overlay of signals wherein the same TCEM may play different roles in different organisms, and the frequency with which a particular TCEM appears influences its effect. The patterns observed provide clues to bacterial immune evasion and to strategies for intervention, including vaccine design. The breadth and distinct frequency patterns of the immunoglobulin-derived peptides suggest a role of immunoglobulins in maintaining a broadly responsive T-cell repertoire.