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Differential immunodominance hierarchy of CD8+ T-cell responses in HLA-B*27: 05- and -B*27:02-mediated control of HIV-1 infection

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Emily Adland
  • Matilda Hill
  • Nora Lavandier
  • Anna Csala
  • Anne Edwards
  • Fabian Chen
  • Marek Radkowski
  • Justyna D. Kowalska
  • Dimitrios Paraskevis
  • Angelos Hatzakis
  • Humberto Valenzuela-Ponce
  • Katja Pfafferott
  • Ian Williams
  • Pierre Pellegrino
  • Persephone Borrow
  • Masahiko Mori
  • Jürgen Rockstroh
  • Julia G. Prado
  • Beatriz Mothe
  • Judith Dalmau
  • Javier Martinez-Picado
  • Gareth Tudor-Williams
  • John Frater
  • Gustavo Reyes Teran
  • Simon Mallal
  • Mina John
  • Susan Buchbinder
  • Gregory Kirk
  • Jeffrey Martin
  • Nelson Michael
  • Jacques Fellay
  • Steve Deeks
  • Bruce Walker
  • Santiago Avila-Rios
  • David Cole
  • Christian Brander
  • Mary Carrington
  • Philip Goulder

The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05- restricted CD8+ T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLAB* 27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02- restricted CD8+ T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8+ T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLAB* 27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8+ T-cell responses that dominate HIV-specific CD8+ T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV.

OriginalsprogEngelsk
Artikelnummere01685-17
TidsskriftJournal of Virology
Vol/bind92
Udgave nummer4
Antal sider14
ISSN0022-538X
DOI
StatusUdgivet - feb. 2018

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