Ancient Use of Ig Variable Domains Contributes Significantly to the TCRδ Repertoire
Ancient Use of Ig Variable Domains Contributes Significantly to the TCRδ Repertoire
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DOI：
10.4049/jimmunol.1900369
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发表时间：
2019-09-01
影响因子：
4.4
通讯作者：
Criscitiello, Michael F.
中科院分区：
文献类型：
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作者：
Deiss, Thaddeus C.;Breaux, Breanna;Criscitiello, Michael F.
在通常研究的哺乳动物中，编码 B 和 T 细胞 Ag 受体的基因座通常是不同的，每个受体的基因片段仅限于位点内顺式染色体重排。铰口鲨 (Ginglymostoma cirratum) 代表最古老的脊椎动物纲，即软骨鱼类，通过 Ig 和 TCR 谱系提供适应性免疫，并且是越来越多利用 Ig-TCR δ 重排融合这些不同谱系的类群中的一个物种。对护士鲨 Ig-TCR delta 库的分析发现，这些重排具有与典型 TCR 重排高度相似的 CDR3 特征。此外，Ig-TCR δ 重排以 TCR γ 表达，典型地在 TCR δ 异二聚体中发现。我们还量化了胸腺中 BCR (IgHV-IgHC)、嵌合 (IgHV-TCR delta C) 和规范 (TCR delta V-TCR delta C) 转录本的 BCR 和 TCR 转录本，发现胸腺和脾脏中的表达水平相同。我们还利用靶向细菌人工染色体测序方法对护士鲨 TCR α δ 基因座进行了表征，发现 TCR δ 基因座包含来自多个谱系的 V 片段复合体。一个类似 IgH 的 V 片段位于护士鲨 TCR δ 易位点内，与我们在系统发育分析中发现的 TCR δ（但不是 IgH）重排表达的 IgHV 样重排分组。这种与 TCR δ 相关的 IgH 样 V 片段的独特谱系被称为“TAILV”。我们的数据说明了动态 TCR δ 库，采用 TCR δ V、NARTCRV、鲨鱼 IgH 簇的真正反式重排，以及 TCR δ 相关 Ig 样 V 片段中的新谱系。
The loci encoding B and T cell Ag receptors are generally distinct in commonly studied mammals, with each receptor's gene segments limited to intralocus, cis chromosomal rearrangements. The nurse shark (Ginglymostoma cirratum) represents the oldest vertebrate class, the cartilaginous fish, with adaptive immunity provided via Ig and TCR lineages, and is one species among a growing number of taxa employing Ig-TCR delta rearrangements that blend these distinct lineages. Analysis of the nurse shark Ig-TCR delta repertoire found that these rearrangements possess CDR3 characteristics highly similar to canonical TCR rearrangements. Furthermore, the Ig-TCR delta rearrangements are expressed with TCR gamma, canonically found in the TCR delta heterodimer. We also quantified BCR and TCR transcripts in the thymus for BCR (IgHV-IgHC), chimeric (IgHV-TCR delta C), and canonical (TCR delta V-TCR delta C) transcripts, finding equivalent expression levels in both thymus and spleen. We also characterized the nurse shark TCR alpha delta locus with a targeted bacterial artifical chromosome sequencing approach and found that the TCR delta locus houses a complex of V segments from multiple lineages. An IgH-like V segment, nestled within the nurse shark TCR delta translocus, grouped with IgHV-like rearrangements we found expressed with TCR delta (but not IgH) rearrangements in our phylogenetic analysis. This distinct lineage of TCR delta-associated IgH-like V segments was termed "TAILVs." Our data illustrate a dynamic TCR delta repertoire employing TCR delta Vs, NARTCRVs, bona fide trans-rearrangements from shark IgH clusters, and a novel lineage in the TCR delta-associated Ig-like V segments.