Dataset Information

A comprehensive analysis of the germline and expressed TCR repertoire in White Peking duck.

ABSTRACT: Recently, many immune-related genes have been extensively studied in ducks, but relatively little is known about their TCR genes. Here, we determined the germline and expressed repertoire of TCR genes in White Peking duck. The genomic organization of the duck TCR?/?, TCR? and unconventional TCR?2 loci are highly conserved with their counterparts in mammals or chickens. By contrast, the duck TCR? locus is organized in an unusual pattern, (V?)n-D?-(J?)2-C?1-(J?)4-C?2, which differs from the tandem-aligned clusters in mammals or the translocon organization in some teleosts. Excluding the first exon encoding the immunoglobulin domain, the subsequent exons of the two C? show significant diversity in nucleotide sequence and exon structure. Based on the nucleotide sequence identity, 49?V?, 30?V?, 13?V? and 15?V? unique gene segments are classified into 3?V?, 5?V?, 4?V? and 6?V? subgroups, respectively. Phylogenetic analyses revealed that most duck V subgroups, excluding V?1, V?5 and V?6, have closely related orthologues in chicken. The coding joints of all cDNA clones demonstrate conserved mechanisms that are used to increase junctional diversity. Collectively, these data provide insight into the evolution of TCRs in vertebrates and improve our understanding of the avian immune system.

SUBMITTER: Yang Z

PROVIDER: S-EPMC5278385 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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A comprehensive analysis of the germline and expressed TCR repertoire in White Peking duck.

Yang Zhi Z Sun Yi Y Ma Yonghe Y Li Zhenrong Z Zhao Yu Y Ren Liming L Han Haitang H Jiang Yunliang Y Zhao Yaofeng Y

Scientific reports 20170130

Recently, many immune-related genes have been extensively studied in ducks, but relatively little is known about their TCR genes. Here, we determined the germline and expressed repertoire of TCR genes in White Peking duck. The genomic organization of the duck TCRα/δ, TCRγ and unconventional TCRδ2 loci are highly conserved with their counterparts in mammals or chickens. By contrast, the duck TCRβ locus is organized in an unusual pattern, (Vβ)n-Dβ-(Jβ)2-Cβ1-(Jβ)4-C ...[more]

PMID: 28134319

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Project description:Infiltrating T-lymphocytes from the peripheral blood into the central nervous system (CNS) play a dynamic role in the development of a neurological immune-mediated diseases. HAM/TSP is a chronic progressive inflammatory neurological disorder associated with human T-cell lymphotropic virus type I (HTLV-I) infection. In this chronic myelopathy, virus-infected circulating T-cells infiltrate the CNS and an immune response is initiated against the components of CNS. As the HTLV-I proviral load (PVL) has been used as the best clinical marker for patient diagnostic with HAM/TSP, we hypothesized there might be a signature on T-cell receptor (TCR) clonal repertoire in these patients, which could distinguish HAM/TSP patients from the healthy population, as well as from patients with a more heterogeneous CNS-reactive inflammatory disease as multiple sclerosis (MS). With this in mind, we applied an innovative unbiased molecular technique – unique molecular identifier (UMI) library-strategy to investigate with high accuracy the TCR clonal repertoire by high throughput sequencing (HTS) technology. cDNA-TCR β-chain libraries were sequenced from 2 million peripheral mononuclear cells (PBMCs) in 14 HAM/TSP patients, 34 MS patients and 20 healthy controls (HC). To address whether the clonal expansion correlates with the patient’s PVL level, analysis of longitudinal TCR repertoire was performed in 2 HAM/TSP patients. Over 5.6 million TCR sequences were generated per sample on HiSeq 2500 Illumina system and analyzed through the molecular identifier groups-based error correction pipeline (MiGEC). Bioinformatic analysis showed that clones with more than 8 reads had a lower coefficient of variation (CV) and then could be used with confidence to evaluate the TCR clonal expansion. While HAM/TSP patients showed the higher clonal T-cell expansion compared to MS and HC, increase of the TCR clonal expansion was inversely correlated with the diversity of TCR repertoire in all subject’s group. In addition, correlation of the PVL with TCR clonal expansion was observed in HAM/TSP patients at longitudinal time-points. Surprisingly, MS patients showed a higher diversity of TCR repertoire along with a very slight clonal T-cell expansion in comparison to either HAM/TSP patients or HC. Despite of the higher TCR clonal expansion in HAM/TSP patients, a non-shared or “private” TCR repertoire was observed in these patients. No clones that shared the same CDR3 amino acid sequences were seen in HC and MS patients. However, a cluster of related CDR3 amino acid sequences were observed for 18 out of 34 MS patients when evaluated by phylogenetic tree analysis. It suggestes that a TCR-repertoire signature might characterize patients with MS. Our findings suggest that even though a unique TCR-b repertoire shapes the immune response in patients with neurological immune-mediated disease, a relatedness on clonal T-cell repertoire exist in MS.

Dataset Information

A comprehensive analysis of the germline and expressed TCR repertoire in White Peking duck.

Publications

A comprehensive analysis of the germline and expressed TCR repertoire in White Peking duck.

Similar Datasets

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