Matthews, Philippa C., Koyanagi, Madoka, Kloverpris, Henrik N., Harndahl, Mikkel, Stryhn, Anette, Akahoshi, Tomohiro, Gatanaga, Hiroyuki, Oka, Shinichi, Juarez Molina, Claudia, Valenzuela Ponce, Humberto, Avila Rios, Santiago, Cole, David  ORCID: https://orcid.org/0000-0003-0028-9396, Carlson, Jonathan, Payne, Rebecca P., Ogwu, Anthony, Bere, Alfred, Ndung'u, Thumbi, Gounder, Kamini, Chen, Fabian, Riddell, Lynn, Luzzi, Graz, Shapiro, Roger, Brander, Christian, Walker, Bruce, Sewell, Andrew K. ORCID: https://orcid.org/0000-0003-3194-3135, Reyes Teran, Gustavo, Heckerman, David, Hunter, Eric, Buus, Søren, Takiguchi, Masafumi and Goulder, Philip J. R.
2012.
Differential clade-specific HLA-B*3501 association with HIV-1 disease outcome is linked to immunogenicity of a single gag epitope.
Journal of Virology
86
(23)
, pp. 12643-12654.
10.1128/JVI.01381-12
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Abstract
The strongest genetic influence on immune control in HIV-1 infection is the HLA class I genotype. Rapid disease progression in B-clade infection has been linked to HLA-B*35 expression, in particular to the less common HLA-B*3502 and HLA-B*3503 subtypes but also to the most prevalent subtype, HLA-B*3501. In these studies we first demonstrated that whereas HLA-B*3501 is associated with a high viral set point in two further B-clade-infected cohorts, in Japan and Mexico, this association does not hold in two large C-clade-infected African cohorts. We tested the hypothesis that clade-specific differences in HLA associations with disease outcomes may be related to distinct targeting of critical CD8+ T-cell epitopes. We observed that only one epitope was significantly targeted differentially, namely, the Gag-specific epitope NPPIPVGDIY (NY10, Gag positions 253 to 262) (P = 2 × 10−5). In common with two other HLA-B*3501-restricted epitopes, in Gag and Nef, that were not targeted differentially, a response toward NY10 was associated with a significantly lower viral set point. Nonimmunogenicity of NY10 in B-clade-infected subjects derives from the Gag-D260E polymorphism present in ∼90% of B-clade sequences, which critically reduces recognition of the Gag NY10 epitope. These data suggest that in spite of any inherent HLA-linked T-cell receptor repertoire differences that may exist, maximizing the breadth of the Gag-specific CD8+ T-cell response, by the addition of even a single epitope, may be of overriding importance in achieving immune control of HIV infection. This distinction is of direct relevance to development of vaccines designed to optimize the anti-HIV CD8+ T-cell response in all individuals, irrespective of HLA type.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Medicine Research Institutes & Centres > Systems Immunity Research Institute (SIURI) |
| Subjects: | Q Science > QR Microbiology > QR180 Immunology R Medicine > R Medicine (General) |
| Additional Information: | Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/0022-538X/ (accessed 25/02/2014) |
| Publisher: | American Society for Microbiology |
| ISSN: | 0022-538X |
| Date of First Compliant Deposit: | 30 March 2016 |
| Last Modified: | 09 May 2023 22:57 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/42340 |
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