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较短的 TCR β 链在胸腺选择和抗原驱动的选择过程中高度富集。

Shorter TCR β-Chains Are Highly Enriched During Thymic Selection and Antigen-Driven Selection.

机构信息

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

College of Materials and Textile, Zhejiang Sci-Tech University, Hangzhou, China.

出版信息

Front Immunol. 2019 Feb 26;10:299. doi: 10.3389/fimmu.2019.00299. eCollection 2019.


DOI:10.3389/fimmu.2019.00299
PMID:30863407
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6399399/
Abstract

The adaptive immune system uses several strategies to generate a repertoire of T cell receptors (TCR) with sufficient diversity to recognize the universe of potential pathogens. However, it remains unclear how differences in the T cell receptor (TCR) contribute to heterogeneity in T cell state. In this study, we used polychromatic flow cytometry to isolate highly pure CD4/CD8 naive and memory T cells, and applied deep sequencing to characterize corresponding TCR β-chain (TCRβ) complementary-determining region 3 (CDR3) repertoires. We find that shorter TCRβ CDR3s with fewer insertions were highly enriched during thymic selection. Antigen-experienced T cells (memory T cells) harbor shorter CDR3s vs. naive T cells. Moreover, the public TCRβ CDR3 clonotypes within cell subsets or interindividual tend to have shorter CDR3 length and a significantly larger size compared with "private" clonotypes. Taken together, shorter CDR3s highly enriched during thymic selection and antigen-driven selection, and further enriched in public T-cell responses. These results indicated that it may be evolutionary pressures drive short CDR3s to recognize most of antigen in nature.

摘要

适应性免疫系统利用多种策略来产生具有足够多样性的 T 细胞受体 (TCR),以识别潜在病原体的整个范围。然而,T 细胞受体 (TCR) 的差异如何导致 T 细胞状态的异质性仍不清楚。在这项研究中,我们使用多色流式细胞术分离高度纯的 CD4/CD8 幼稚和记忆 T 细胞,并应用深度测序来描述相应的 TCR β 链 (TCRβ) 互补决定区 3 (CDR3) 库。我们发现,在胸腺选择过程中,较短的 TCRβ CDR3 具有较少的插入序列高度富集。与幼稚 T 细胞相比,抗原经验丰富的 T 细胞(记忆 T 细胞)具有较短的 CDR3。此外,细胞亚群或个体间的公共 TCRβ CDR3 克隆型与“私有”克隆型相比,其 CDR3 长度较短,且大小显著增大。综上所述,较短的 CDR3 在胸腺选择和抗原驱动的选择过程中高度富集,并且在公共 T 细胞反应中进一步富集。这些结果表明,可能是进化压力促使短 CDR3 识别自然界中大多数抗原。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6249/6399399/d1eba9bfff03/fimmu-10-00299-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6249/6399399/cf8e68ab7d1d/fimmu-10-00299-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6249/6399399/83c07f1940e1/fimmu-10-00299-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6249/6399399/a371fa779ec1/fimmu-10-00299-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6249/6399399/f131019b427a/fimmu-10-00299-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6249/6399399/c382389b0614/fimmu-10-00299-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6249/6399399/58a6f6c0ca76/fimmu-10-00299-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6249/6399399/d1eba9bfff03/fimmu-10-00299-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6249/6399399/cf8e68ab7d1d/fimmu-10-00299-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6249/6399399/83c07f1940e1/fimmu-10-00299-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6249/6399399/a371fa779ec1/fimmu-10-00299-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6249/6399399/f131019b427a/fimmu-10-00299-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6249/6399399/c382389b0614/fimmu-10-00299-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6249/6399399/58a6f6c0ca76/fimmu-10-00299-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6249/6399399/d1eba9bfff03/fimmu-10-00299-g0007.jpg

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本文引用的文献

[1]
Public Clonotypes and Convergent Recombination Characterize the Naïve CD8 T-Cell Receptor Repertoire of Extremely Preterm Neonates.

Front Immunol. 2017-12-19

[2]
T cell receptor β-chains display abnormal shortening and repertoire sharing in type 1 diabetes.

Nat Commun. 2017-11-27

[3]
Targeted reconstruction of T cell receptor sequence from single cell RNA-seq links CDR3 length to T cell differentiation state.

Nucleic Acids Res. 2017-9-19

[4]
Analysis of the CDR3 length repertoire and the diversity of T cell receptor α and β chains in swine CD4+ and CD8+ T lymphocytes.

Mol Med Rep. 2017-7

[5]
Analysis of the Repertoire Features of TCR Beta Chain CDR3 in Human by High-Throughput Sequencing.

Cell Physiol Biochem. 2016

[6]
Current status and recent advances of next generation sequencing techniques in immunological repertoire.

Genes Immun. 2016-3-10

[7]
TCRβ repertoire of CD4+ and CD8+ T cells is distinct in richness, distribution, and CDR3 amino acid composition.

J Leukoc Biol. 2016-3

[8]
High-throughput T-cell receptor sequencing across chronic liver diseases reveals distinct disease-associated repertoires.

Hepatology. 2015-9-30

[9]
Composition and variation analysis of the TCR β-chain CDR3 repertoire in systemic lupus erythematosus using high-throughput sequencing.

Mol Immunol. 2015-10

[10]
Transcription factors and target genes of pre-TCR signaling.

Cell Mol Life Sci. 2015-6

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