Complex T-Cell Receptor Repertoire Dynamics Underlie the CD8 + T-Cell Response to HIV-1

• Published in: Journal of virology Vol. 89; no. 1; pp. 110 - 119
• Main Authors: Costa, Ana I., Koning, Dan, Ladell, Kristin, McLaren, James E., Grady, Bart P. X., Schellens, Ingrid M. M., van Ham, Petra, Nijhuis, Monique, Borghans, José A. M., Keşmir, Can, Price, David A., van Baarle, Debbie
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.01.2015
• Subjects: Adaptation, Biological; CD8-Positive T-Lymphocytes - immunology; Cohort Studies; Epitopes - immunology; HIV-1 - immunology; Human immunodeficiency virus 1; Humans; Immune Evasion; Lentivirus; Pathogenesis and Immunity; Receptors, Antigen, T-Cell - metabolism; T-Lymphocyte Subsets - immunology
• ISSN: 0022-538X; 1098-5514; 1098-5514
• DOI: 10.1128/JVI.01765-14

Although CD8 + T cells are important for the control of HIV-1 in vivo , the precise correlates of immune efficacy remain unclear. In this study, we conducted a comprehensive analysis of viral sequence variation and T-cell receptor (TCR) repertoire composition across multiple epitope specificities in a group of antiretroviral treatment-naive individuals chronically infected with HIV-1. A negative correlation was detected between changes in antigen-specific TCR repertoire diversity and CD8 + T-cell response magnitude, reflecting clonotypic expansions and contractions related to alterations in cognate viral epitope sequences. These patterns were independent of the individual, as evidenced by discordant clonotype-specific transitions directed against different epitopes in single subjects. Moreover, long-term asymptomatic HIV-1 infection was characterized by evolution of the TCR repertoire in parallel with viral replication. Collectively, these data suggest a continuous bidirectional process of adaptation between HIV-1 and virus-specific CD8 + T-cell clonotypes orchestrated at the TCR-antigen interface. IMPORTANCE We describe a relation between viral epitope mutation, antigen-specific T-cell expansion, and the repertoire of responding clonotypes in chronic HIV-1 infection. This work provides insights into the process of coadaptation between the human immune system and a rapidly evolving lentivirus.