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.
Front Immunol. 2019 Feb 26;10:299. doi: 10.3389/fimmu.2019.00299. eCollection 2019.
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.
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。
Front Immunol. 2019-2-26
Arthritis Res Ther. 2019-12-19
iScience. 2024-9-16
Front Immunol. 2022
Cell Physiol Biochem. 2016
Cell Mol Life Sci. 2015-6