title: 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-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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Laboratory for Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Costa
authors.affiliation: Laboratory for Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Dan
authors.initials: D
authors.lastname: Koning
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.
authors.forename: Kristin
authors.initials: K
authors.lastname: Ladell
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.
authors.forename: James E
authors.initials: JE
authors.lastname: McLaren
authors.affiliation: Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Bart P X
authors.initials: BP
authors.lastname: Grady
authors.affiliation: Laboratory for Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Ingrid M M
authors.initials: IM
authors.lastname: Schellens
authors.affiliation: Department of Virology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: van Ham
authors.affiliation: Department of Virology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: Nijhuis
authors.affiliation: Laboratory for Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: José A M
authors.initials: JA
authors.lastname: Borghans
authors.affiliation: Department of Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, The Netherlands.
authors.forename: Can
authors.initials: C
authors.lastname: Keşmir
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.affiliation: Laboratory for Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands debbie.van.baarle@rivm.nl.
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
mesh_terms: D000220:Adaptation, Biological; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D000939:Epitopes / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D000939:Epitopes; D011948:Receptors, Antigen, T-Cell