The effect of HLA polymorphisms on the recognition of Gag epitopes in HIV-1 CRF01_AE infection.
INTRODUCTION: The design of a globally effective vaccine rests on the identification of epitopes capable of eliciting effective cytotoxic T lymphocyte (CTL) responses across multiple HIV clades in different populations. This study aims to discern the effect of HLA polymorphisms and the cross-clade r...
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doaj-e7f9c2c452bb45dfb66cc92bf06d000d2020-11-25T01:26:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0177e4169610.1371/journal.pone.0041696The effect of HLA polymorphisms on the recognition of Gag epitopes in HIV-1 CRF01_AE infection.Busarawan SriwanthanaMasahiko MoriMari TanakaSei NishimuraToshiyuki MiuraPanita PathipvanichPathom SawanpanyalertKoya AriyoshiINTRODUCTION: The design of a globally effective vaccine rests on the identification of epitopes capable of eliciting effective cytotoxic T lymphocyte (CTL) responses across multiple HIV clades in different populations. This study aims to discern the effect of HLA polymorphisms and the cross-clade reactivity or clade-specificity of epitopes in Thailand where HIV-1 CRF01_AE is circulating. MATERIALS AND METHODS: 14 peptides based on consensus HIV-1 CRF01_AE amino acid sequences were designed for use in IFN-γ ELISpot assays and (51)Cr release assays among 66 HIV-1 CRF01_AE-infected Thai patients. For ELISpot responders carrying HLA alleles currently unknown to restrict CRF01_AE epitopes, in silico epitope-HLA prediction was performed. RESULTS: 29/66 (43.9%) patients recognized at least one peptide. In total 79 responses were seen against all 14 peptides. 28/79 (35.4%) of the responses were in patients with HLA alleles previously reported to restrict CRF01_AE epitopes, 24/79 (30.4%) responses were in individuals with HLA alleles previously reported to restrict epitopes of HIV clades other than CRF01_AE, and the remaining 27/79 (34.2%) responses were not associated with HLA alleles previously known to restrict HIV epitopes. In silico epitope prediction detected 19 novel, epitope-HLA combinations, and 11/19 (57.9%) were associated with HLA-C alleles. We further confirmed a novel HLA restriction of a previously identified HIV-1 Gag epitope [p24(122-130): PPIPVGDIY (PY9)] by HLA-B*40:01 with a standard (51)Cr release assay. DISCUSSION: CTL recognition sites in HIV-1 Gag were similar among different clades but the HLA restriction differed in Thai patients. This disparity in HLA restriction along different populations illustrated the importance of clade- and population-specific HLA analysis prior to CTL vaccine design.http://europepmc.org/articles/PMC3407236?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Busarawan Sriwanthana Masahiko Mori Mari Tanaka Sei Nishimura Toshiyuki Miura Panita Pathipvanich Pathom Sawanpanyalert Koya Ariyoshi |
spellingShingle |
Busarawan Sriwanthana Masahiko Mori Mari Tanaka Sei Nishimura Toshiyuki Miura Panita Pathipvanich Pathom Sawanpanyalert Koya Ariyoshi The effect of HLA polymorphisms on the recognition of Gag epitopes in HIV-1 CRF01_AE infection. PLoS ONE |
author_facet |
Busarawan Sriwanthana Masahiko Mori Mari Tanaka Sei Nishimura Toshiyuki Miura Panita Pathipvanich Pathom Sawanpanyalert Koya Ariyoshi |
author_sort |
Busarawan Sriwanthana |
title |
The effect of HLA polymorphisms on the recognition of Gag epitopes in HIV-1 CRF01_AE infection. |
title_short |
The effect of HLA polymorphisms on the recognition of Gag epitopes in HIV-1 CRF01_AE infection. |
title_full |
The effect of HLA polymorphisms on the recognition of Gag epitopes in HIV-1 CRF01_AE infection. |
title_fullStr |
The effect of HLA polymorphisms on the recognition of Gag epitopes in HIV-1 CRF01_AE infection. |
title_full_unstemmed |
The effect of HLA polymorphisms on the recognition of Gag epitopes in HIV-1 CRF01_AE infection. |
title_sort |
effect of hla polymorphisms on the recognition of gag epitopes in hiv-1 crf01_ae infection. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
INTRODUCTION: The design of a globally effective vaccine rests on the identification of epitopes capable of eliciting effective cytotoxic T lymphocyte (CTL) responses across multiple HIV clades in different populations. This study aims to discern the effect of HLA polymorphisms and the cross-clade reactivity or clade-specificity of epitopes in Thailand where HIV-1 CRF01_AE is circulating. MATERIALS AND METHODS: 14 peptides based on consensus HIV-1 CRF01_AE amino acid sequences were designed for use in IFN-γ ELISpot assays and (51)Cr release assays among 66 HIV-1 CRF01_AE-infected Thai patients. For ELISpot responders carrying HLA alleles currently unknown to restrict CRF01_AE epitopes, in silico epitope-HLA prediction was performed. RESULTS: 29/66 (43.9%) patients recognized at least one peptide. In total 79 responses were seen against all 14 peptides. 28/79 (35.4%) of the responses were in patients with HLA alleles previously reported to restrict CRF01_AE epitopes, 24/79 (30.4%) responses were in individuals with HLA alleles previously reported to restrict epitopes of HIV clades other than CRF01_AE, and the remaining 27/79 (34.2%) responses were not associated with HLA alleles previously known to restrict HIV epitopes. In silico epitope prediction detected 19 novel, epitope-HLA combinations, and 11/19 (57.9%) were associated with HLA-C alleles. We further confirmed a novel HLA restriction of a previously identified HIV-1 Gag epitope [p24(122-130): PPIPVGDIY (PY9)] by HLA-B*40:01 with a standard (51)Cr release assay. DISCUSSION: CTL recognition sites in HIV-1 Gag were similar among different clades but the HLA restriction differed in Thai patients. This disparity in HLA restriction along different populations illustrated the importance of clade- and population-specific HLA analysis prior to CTL vaccine design. |
url |
http://europepmc.org/articles/PMC3407236?pdf=render |
work_keys_str_mv |
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