1. Partial recovery of disturbed V-J pairing profiles of T-cell receptor in people living with HIV receiving long-term antiretroviral therapy
- Author
-
Fujie Zhang, Yongqin Zeng, Guoli Li, Jiarui Li, Yu Hao, Bei Li, Chen Chen, Henghui Zhang, Liuluan Zhu, Chuan Song, Juan Du, Di Liu, Hui Zeng, Yu Zhang, Hongxin Zhao, Junyan Han, and Rui Li
- Subjects
Adult ,CD4-Positive T-Lymphocytes ,Male ,0301 basic medicine ,Time Factors ,Receptors, Antigen, T-Cell, alpha-beta ,antiretroviral therapy ,Immunoglobulin Variable Region ,Receptors, Antigen, T-Cell ,Human immunodeficiency virus (HIV) ,HIV Infections ,Complementarity determining region ,Biology ,medicine.disease_cause ,acquired immune deficiency syndrome ,General Biochemistry, Genetics and Molecular Biology ,V-J pairing ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,General Environmental Science ,human immunodeficiency virus ,Repertoire ,T-cell receptor ,Tcr repertoire ,Complementarity Determining Regions ,Antiretroviral therapy ,CD4 Lymphocyte Count ,Tenth percentile ,030104 developmental biology ,Anti-Retroviral Agents ,030220 oncology & carcinogenesis ,Pairing ,Immunology ,Immunoglobulin Joining Region ,Female ,T cell receptor ,General Agricultural and Biological Sciences ,Immunologic Memory ,Research Paper - 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.
- Published
- 2020