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

摘要

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 na?ve and memory CD4~+T cells in healthy donors, HIV-infected antiretroviral therapy(ART)-na?ve patients and long-term(over5 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-na?ve 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.