Large-scale screening of HIV-1 T-cell epitopes restricted by 12 prevalent HLA-A allotypes in Northeast Asia and universal detection of HIV-1-specific CD8+ T cells
BackgroundAlthough the immune response of host T cells to human immunodeficiency virus (HIV) significantly influences the progression of the infection, the development of T-cell-based vaccines and therapies, as well as the clinical evaluation of specific T-cell functions, is currently markedly hinde...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1529721/full |
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| Summary: | BackgroundAlthough the immune response of host T cells to human immunodeficiency virus (HIV) significantly influences the progression of the infection, the development of T-cell-based vaccines and therapies, as well as the clinical evaluation of specific T-cell functions, is currently markedly hindered by the absence of broad-spectrum, functionally validated HIV T-cell epitopes that account for the polymorphisms of the human leukocyte antigen (HLA) within an indicated geographic population. This study aimed to identify T-cell epitopes derived from the GP160, GAG, and POL proteins of the HIV-1 strain, specifically linked to 12 prevalent HLA-A allotypes, that collectively represent approximately 91% of the total gene frequency in Northeast Asian populations.MethodsA total of 134 epitopes were predicted in silico and selected as potential candidates for further validation. Subsequently, peripheral blood mononuclear cells (PBMCs) were collected from 96 individuals with HIV-1 and cocultured ex vivo with each epitope candidate peptide, followed by the detection of activated CD8+ T cells. Peripheral blood mononuclear cells (PBMCs) were collected from 96 individuals with HIV-1 and cocultured ex vivo with each candidate peptide epitope, followed by the detection of activated CD8+ T cells. A total of 69 epitopes were validated as real-world HIV T-cell epitopes presented by 12 dominant HLA-A allotypes. Furthermore, the HLA-A cross-restriction for each epitope candidate was identified through peptide competitive binding assays using 12 transfected HMy2.CIR cell lines.ResultsA total of 45 epitopes demonstrated high affinity, while 31 epitopes displayed intermediate affinity. A broad-spectrum CD8+ T-cell epitope library containing 141 validated epitope peptides was used to universally detect HIV-1-specific CD8+ T cells via peptide-PBMC ex vivo coculture and intracellular IFN-γ staining. In 52 people with HIV-1, the number of reactive HIV-1 specific CD8+ T cells was significantly higher in the CD4+ T-cell-high patient group compared to the CD4+ T-cell-low patient group, and it correlated with the CD4+ T-cell-low patient group (<200/μL).ConclusionThis study provides a broad-spectrum CD8+ T-cell epitope library aimed at developing a T-cell-directed HIV vaccine that offers high population coverage in Northeast Asia. In addition, it establishes a universal detection method for the clinical assessment of HIV-1-specific CD8+ T-cell responses. |
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| ISSN: | 1664-302X |