Multilayered HIV-1 gag-specific T-cell responses contribute to slow progression in HLA-A*30-B*13-C*06-positive patients. (1st June 2015)

• Record Type: Journal Article
• Authors: Zhang, Hui; Han, Xiaoxu; Zhao, Bin; An, Minghui; Wang, Zhe; Jiang, Fanming; Xu, Junjie; Zhang, Zining; Dong, Tao; Shang, Hong
• Is Part Of: AIDS. Volume 29:Number 9(2015)
• Publication Date: 2015-06-01
• Subjects: AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000000652
• Languages: English
• ISSNs: 0269-9370

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objective:</title> <p>The HLA-A<sup>*</sup>30-B<sup>*</sup>13-C<sup>*</sup>06 haplotype is reported to be associated with slow disease progression in the HIV-1-infected Northern Han Chinese population, but the mechanism remains unknown.</p> </sec> <sec> <title>Design:</title> <p>Gag-specific T-cell responses and gag sequencing were performed in nine B′ clade HIV-1-infected HLA-A<sup>*</sup>30-B<sup>*</sup>13-C<sup>*</sup>06-positive slow progressors to understand HLA-associated viral control.</p> </sec> <sec> <title>Methods:</title> <p>Interferon-γ ELISPOT assays were performed to determine the Gag-specific T-cell responses and cross-reactivity to variant peptides. Longitudinal HIV-1 gag sequencing was performed at the clonal level.</p> </sec> <sec> <title>Results:</title> <p>The overlapping peptides (OLP)-48: RQANFLGKIWPSHKGRPGNF (RL42 Gag<sub>434-453</sub>); OLP-2: GQLDRWEKIRLRPGGKKKYR (RL42 Gag<sub>11-30</sub>); OLP-15: VQNLQGQMVHQPISPRTLNA (RL42 Gag<sub>135-154</sub>) and OLP-16: HQPISPRTLNAWVKVVEEKA (RL42 Gag<sub>144-163</sub>) were dominant in HLA-A<sup>*</sup>30-B<sup>*</sup>13-C<sup>*</sup>06-positive patients. A new epitope [HQPISPRTL (Gag<sub>144-152</sub>, HL9)] within OLP-15 and OLP-16 was identified. Results showed that strong cross-reactive responses to multiple immunodominant peptides were associated with better clinical outcomes. In addition, efficient cross-recognition of HL9 autologous variants developed in patients was associated with high CD4<sup>+</sup> T-cell counts. However, two patients who had developed mutations to their dominant responses during the follow-up experienced decrease in CD4<sup>+</sup> T-cell counts. It appears that Gag-specific T-cell responses against one or more unmutated epitopes or cross-recognition of autologous epitope variants contribute to slow disease progression in HLA-A<sup>*</sup>30-B<sup>*</sup>13-C<sup>*</sup>06-positive patients.</p> </sec> <sec> <title>Conclusion:</title> <p>We conclude that a single 'appropriate' Gag-specific T-cell response appears to be sufficient to protect patients from disease progression. HLA-A<sup>*</sup>30-B<sup>*</sup>13-C<sup>*</sup>06-positive individuals benefited from having a choice of numerous immunodominant gag epitopes for T cells to react. The study offers new insight for future design of T-cell-based HIV-1 vaccine.</p> </sec> </abstract>