Complex T-cell receptor repertoire dynamics underlie the CD8+ T-cell response to HIV-1

J Virol. 2015 Jan;89(1):110-9. doi: 10.1128/JVI.01765-14. Epub 2014 Oct 15.

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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Biological
  • CD8-Positive T-Lymphocytes / immunology*
  • Cohort Studies
  • Epitopes / immunology*
  • HIV-1 / immunology*
  • Humans
  • Immune Evasion
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocyte Subsets / immunology

Substances

  • Epitopes
  • Receptors, Antigen, T-Cell