4.5 Article

Exploiting knowledge of immune selection in HIV-1 to detect HIV-specific CD8 T-cell responses

Journal

VACCINE
Volume 28, Issue 37, Pages 6052-6057

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2010.06.091

Keywords

CD8 T cells; HLA alleles; HIV-1

Funding

  1. National Institute of Allergy and Infectious Diseases [RO1 AI060460]
  2. Australian National Health and Medical Research Council [ID 384702]
  3. Bill & Melinda Gates Foundation

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Since HLA-restricted cytotoxic T-cell responses select specific polymorphisms in HIV-1 sequences and HLA diversity is relatively static in human populations, we investigated the use of peptide epitopes based on sites of HLA-associated adaptation in HIV-1 sequences to stimulate and detect T-cell responses ex vivo. These HLA-optimised peptides captured more HIV-1 Nef-specific responses compared with overlapping peptides of a single consensus sequence, in interferon-gamma enzyme linked immunospot assays. Sites of immune selection can reveal more immunogenic epitopes in HLA-diverse populations and offer insights into the nature of HLA-epitope targeting, which could be applied in vaccine design. (C) 2010 Elsevier Ltd. All rights reserved.

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