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

Ana I Costa, Dan Koning, Kristin Ladell, James E McLaren, Bart P X Grady, Ingrid M M Schellens, Petra van Ham, Monique Nijhuis, José A M Borghans, Can Keşmir, David A Price, Debbie van Baarle*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Scopus)
26 Downloads (Pure)

Abstract

UNLABELLED: 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.

Original languageEnglish
Pages (from-to)110-9
Number of pages10
JournalJournal of Virology
Volume89
Issue number1
DOIs
Publication statusPublished - Jan-2015
Externally publishedYes

Keywords

  • 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

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