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. 2020 Jun 18;64(1):152–161. doi: 10.1007/s11427-020-1718-2

Partial recovery of disturbed V-J pairing profiles of T-cell receptor in people living with HIV receiving long-term antiretroviral therapy

Guoli Li 1,2, Jiarui Li 1,2, Henghui Zhang 1,2, Yu Zhang 3, Di Liu 4,5, Yu Hao 1,2, Junyan Han 1,2, Juan Du 1,2, Liuluan Zhu 1,2, Yongqin Zeng 3, Bei Li 3, Rui Li 1,2, Chuan Song 1,2, Fujie Zhang 3, Chen Chen 1,2,✉, Hongxin Zhao 3,✉, Hui Zeng 1,2,✉
PMCID: PMC7306449  PMID: 32567004

Abstract

Chronic human immunodeficiency virus (HIV) infection not only causes a gradual loss of CD4+ T cells but also leads to a disturbance of the T cell receptor (TCR) repertoire. In people living with HIV (PLWH), monitoring TCR repertoire is challenged by the inconsistency of complementarity determining region 3 (CDR3) and limited cell numbers in clinical samples. Thus, a quantitative method is necessary for monitoring the TCR repertoire in PLWH. We characterized the TCR V-J pairing profile of naïve and memory CD4+ T cells in healthy donors, HIV-infected antiretroviral therapy (ART)-naïve patients and long-term (over 5 years) ART-experienced patients by performing TCR sequencing. We developed a V-J index with 18 parameters which were subdivided into five categories (expression coverage, cumulative percentage of the top tenth percentile, diversity, intra-individual similarity and inter-individual similarity). In ART-naïve patients, 14 of the 18 parameters were significantly altered. Long-term ART recovered ten parameters. The four unrecovered parameters were related to inter-individual similarity. Therefore, these findings indicate that long-term ART could only partially recover TCR V-J pairs and introduce newly impacted V-J pairs. Moreover, these results provide new insights into the V-J pairing of the TCR and into the disturbance of TCR repertoire in HIV infection.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s11427-020-1718-2 and is accessible for authorized users.

Keywords: acquired immune deficiency syndrome, human immunodeficiency virus, antiretroviral therapy, T cell receptor, V-J pairing

Electronic supplementary material

11427_2020_1718_MOESM1_ESM.pdf (249KB, pdf)

Supplementary material, approximately 249 KB.

11427_2020_1718_MOESM2_ESM.pdf (307.8KB, pdf)

Supplementary material, approximately 307 KB.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (81371804, 81772123 and 81672000), the Thirteen-fifth Key Project (2018ZX10715-005), Beijing Municipal Science and Technology Commission (Z191100006619045) and Beijing Hospital authority (DFL20191801 and DFL20191802). We thank the patients and healthy donors for their involvement in our study. We thank Xue Song at Beijing Genecast Biotechnology Co. for data analysis. We also thank Mr. Gang Wan at Beijing Ditan Hospital, Capital Medical University for valuable advice on statistics.

Compliance and ethics The author(s) declare that they have no conflict of interest.

Contributor Information

Chen Chen, Email: chenchen1@ccmu.edu.cn.

Hongxin Zhao, Email: Drzhao66@ccmu.edu.cn.

Hui Zeng, Email: zenghui@ccmu.edu.cn.

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11427_2020_1718_MOESM1_ESM.pdf (249KB, pdf)

Supplementary material, approximately 249 KB.

11427_2020_1718_MOESM2_ESM.pdf (307.8KB, pdf)

Supplementary material, approximately 307 KB.

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