Contribution of proteasome-catalyzed peptide cis-splicing to viral targeting by CD8+ T cells in HIV-1 infection
Peptides generated by proteasome-catalyzed splicing of noncontiguous amino acid sequences have been shown to constitute a source of nontemplated human leukocyte antigen class I (HLA-I) epitopes, but their role in pathogen-specific immunity remains unknown. CD8+ T cells are key mediators of HIV type...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Published: |
National Academy of Sciences
2019
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| _version_ | 1826282625986199552 |
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| author | Paes, W Leonov, G Partridge, T Frangou, A Brackenridge, S Nicastri, A Parker, R McMichael, A Ternette, N Borrow, P |
| author_facet | Paes, W Leonov, G Partridge, T Frangou, A Brackenridge, S Nicastri, A Parker, R McMichael, A Ternette, N Borrow, P |
| author_sort | Paes, W |
| collection | OXFORD |
| description | Peptides generated by proteasome-catalyzed splicing of noncontiguous amino acid sequences have been shown to constitute a source of nontemplated human leukocyte antigen class I (HLA-I) epitopes, but their role in pathogen-specific immunity remains unknown. CD8+ T cells are key mediators of HIV type 1 (HIV-1) control, and identification of novel epitopes to enhance targeting of infected cells is a priority for prophylactic and therapeutic strategies. To explore the contribution of proteasome-catalyzed peptide splicing (PCPS) to HIV-1 epitope generation, we developed a broadly applicable mass spectrometry-based discovery workflow that we employed to identify spliced HLA-I–bound peptides on HIV-infected cells. We demonstrate that HIV-1–derived spliced peptides comprise a relatively minor component of the HLA-I–bound viral immunopeptidome. Although spliced HIV-1 peptides may elicit CD8+ T cell responses relatively infrequently during infection, CD8+ T cells primed by partially overlapping contiguous epitopes in HIV-infected individuals were able to cross-recognize spliced viral peptides, suggesting a potential role for PCPS in restricting HIV-1 escape pathways. Vaccine-mediated priming of responses to spliced HIV-1 epitopes could thus provide a novel means of exploiting epitope targets typically underutilized during natural infection. |
| first_indexed | 2024-03-07T00:46:41Z |
| format | Journal article |
| id | oxford-uuid:84eb23aa-2d93-47c9-a3a4-bd2822ba84b6 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T00:46:41Z |
| publishDate | 2019 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:84eb23aa-2d93-47c9-a3a4-bd2822ba84b62022-03-26T21:54:10ZContribution of proteasome-catalyzed peptide cis-splicing to viral targeting by CD8+ T cells in HIV-1 infectionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:84eb23aa-2d93-47c9-a3a4-bd2822ba84b6Symplectic Elements at OxfordNational Academy of Sciences2019Paes, WLeonov, GPartridge, TFrangou, ABrackenridge, SNicastri, AParker, RMcMichael, ATernette, NBorrow, PPeptides generated by proteasome-catalyzed splicing of noncontiguous amino acid sequences have been shown to constitute a source of nontemplated human leukocyte antigen class I (HLA-I) epitopes, but their role in pathogen-specific immunity remains unknown. CD8+ T cells are key mediators of HIV type 1 (HIV-1) control, and identification of novel epitopes to enhance targeting of infected cells is a priority for prophylactic and therapeutic strategies. To explore the contribution of proteasome-catalyzed peptide splicing (PCPS) to HIV-1 epitope generation, we developed a broadly applicable mass spectrometry-based discovery workflow that we employed to identify spliced HLA-I–bound peptides on HIV-infected cells. We demonstrate that HIV-1–derived spliced peptides comprise a relatively minor component of the HLA-I–bound viral immunopeptidome. Although spliced HIV-1 peptides may elicit CD8+ T cell responses relatively infrequently during infection, CD8+ T cells primed by partially overlapping contiguous epitopes in HIV-infected individuals were able to cross-recognize spliced viral peptides, suggesting a potential role for PCPS in restricting HIV-1 escape pathways. Vaccine-mediated priming of responses to spliced HIV-1 epitopes could thus provide a novel means of exploiting epitope targets typically underutilized during natural infection. |
| spellingShingle | Paes, W Leonov, G Partridge, T Frangou, A Brackenridge, S Nicastri, A Parker, R McMichael, A Ternette, N Borrow, P Contribution of proteasome-catalyzed peptide cis-splicing to viral targeting by CD8+ T cells in HIV-1 infection |
| title | Contribution of proteasome-catalyzed peptide cis-splicing to viral targeting by CD8+ T cells in HIV-1 infection |
| title_full | Contribution of proteasome-catalyzed peptide cis-splicing to viral targeting by CD8+ T cells in HIV-1 infection |
| title_fullStr | Contribution of proteasome-catalyzed peptide cis-splicing to viral targeting by CD8+ T cells in HIV-1 infection |
| title_full_unstemmed | Contribution of proteasome-catalyzed peptide cis-splicing to viral targeting by CD8+ T cells in HIV-1 infection |
| title_short | Contribution of proteasome-catalyzed peptide cis-splicing to viral targeting by CD8+ T cells in HIV-1 infection |
| title_sort | contribution of proteasome catalyzed peptide cis splicing to viral targeting by cd8 t cells in hiv 1 infection |
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