Paes, W;
Leonov, G;
Partridge, T;
Chikata, T;
Murakoshi, H;
Frangou, A;
Brackenridge, S;
... Borrow, P; + view all
(2019)
Contribution of proteasome-catalyzed peptide cis-splicing to viral targeting by CD8⁺ T cells in HIV-1 infection.
Proceedings of the National Academy of Sciences of the United States of America
, 116
(49)
pp. 24748-24759.
10.1073/pnas.1911622116.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Contribution of proteasome-catalyzed peptide cis-splicing to viral targeting by CD8⁺ T cells in HIV-1 infection |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1073/pnas.1911622116 |
| Publisher version: | https://doi.org/10.1073/pnas.1911622116 |
| Language: | English |
| Additional information: | © 2019 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | T cell epitope, human immunodeficiency virus, immunopeptidome, peptide splicing, proteasome |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10091215 |
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