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

Abstract

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-naïve 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, evidenced by discordant clonotype-specific evolution 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 provide insights into the process of co-adaptation between the human immune system and a rapidly evolving lentivirus.