Identification of immunodominant HIV-1 epitopes presented by 2 HLA-C*12:02, a protective allele, using an immunopeptidomics 3 approach
<jats:p>Despite the fact that cell-surface expression of HLA-C on both uninfected and HIV-infected cells is lower than that of HLA-A and -B, increasing evidence suggests an important role for HLA-C and HLA-C-restricted CD8<jats:sup>+</jats:sup> T cell responses in determining the e...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Society for Microbiology
2019
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| _version_ | 1826280901362843648 |
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| author | Chikata, T Paes, W Akahoshi, T Partridge, T Murakoshi, H Gatanaga, H Ternette, N Oka, S Borrow, P Takiguchi, M |
| author_facet | Chikata, T Paes, W Akahoshi, T Partridge, T Murakoshi, H Gatanaga, H Ternette, N Oka, S Borrow, P Takiguchi, M |
| author_sort | Chikata, T |
| collection | OXFORD |
| description | <jats:p>Despite the fact that cell-surface expression of HLA-C on both uninfected and HIV-infected cells is lower than that of HLA-A and -B, increasing evidence suggests an important role for HLA-C and HLA-C-restricted CD8<jats:sup>+</jats:sup> T cell responses in determining the efficiency of viral control in HIV-1-infected individuals. Nonetheless, HLA-C-restricted T cell responses are much less well-studied than HLA-A/B-restricted ones, and relatively few optimal HIV-1 CD8<jats:sup>+</jats:sup> T cell epitopes restricted by HLA-C alleles have been defined. Recent improvements in the sensitivity of mass spectrometry (MS)-based approaches for profiling the immunopeptidome present an opportunity for epitope discovery on a large scale. Here, we employed a mass spectrometry (MS)-based immunopeptidomic strategy to characterize HIV-1 peptides presented by a protective allele, HLA-C*12:02. We identified a total of 10,799 unique 8-12-mer peptides, including 15 HIV-1 peptides. The latter included 2 previously-reported immunodominant HIV-1 epitopes; and analysis of T cell responses to the other HIV-1 peptides detected revealed an additional immunodominant epitope. These findings illustrate the utility of MS-based approaches for epitope definition, and emphasize the capacity of HLA-C to present immunodominant T cell epitopes in HIV-infected individuals, indicating the importance of further evaluation of HLA-C-restricted responses to identify novel targets for HIV-1 prophylactic and therapeutic strategies.</jats:p> <jats:p><jats:bold>IMPORTANCE</jats:bold> Mass spectrometry (MS)-based approaches are increasingly being employed for large-scale identification of HLA-bound peptides derived from pathogens, but only very limited profiling of the HIV-1 immunopeptidome has been conducted to date. Notably, a growing body of evidence has recently begun to indicate a protective role for HLA-C in HIV-1 infection, which may suggest that despite the fact that levels of HLA-C expression on both uninfected and HIV-1-infected cells are lower than those of HLA-A/B, HLA-C still presents epitopes to CD8<jats:sup>+</jats:sup> T cells effectively. To explore this, we analyzed HLA-C*12:02-restricted HIV-1 peptides presented on HIV-1-infected cells expressing only HLA-C*12:02 (a protective allele) using LC-MS/MS. We identified a number of novel HLA-C*12:02-bound HIV-1 peptides, and showed that although the majority of them did not elicit T cell responses during natural infection in a Japanese cohort, they included three immunodominant epitopes, emphasizing the contribution of HLA-C to epitope presentation on HIV-infected cells.</jats:p> |
| first_indexed | 2024-03-07T00:20:42Z |
| format | Journal article |
| id | oxford-uuid:7c704843-d47d-4e2c-b164-1b30c3b85148 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:20:42Z |
| publishDate | 2019 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | oxford-uuid:7c704843-d47d-4e2c-b164-1b30c3b851482022-03-26T20:57:05Z Identification of immunodominant HIV-1 epitopes presented by 2 HLA-C*12:02, a protective allele, using an immunopeptidomics 3 approachJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7c704843-d47d-4e2c-b164-1b30c3b85148EnglishSymplectic Elements at OxfordAmerican Society for Microbiology2019Chikata, TPaes, WAkahoshi, TPartridge, TMurakoshi, HGatanaga, HTernette, NOka, SBorrow, PTakiguchi, M<jats:p>Despite the fact that cell-surface expression of HLA-C on both uninfected and HIV-infected cells is lower than that of HLA-A and -B, increasing evidence suggests an important role for HLA-C and HLA-C-restricted CD8<jats:sup>+</jats:sup> T cell responses in determining the efficiency of viral control in HIV-1-infected individuals. Nonetheless, HLA-C-restricted T cell responses are much less well-studied than HLA-A/B-restricted ones, and relatively few optimal HIV-1 CD8<jats:sup>+</jats:sup> T cell epitopes restricted by HLA-C alleles have been defined. Recent improvements in the sensitivity of mass spectrometry (MS)-based approaches for profiling the immunopeptidome present an opportunity for epitope discovery on a large scale. Here, we employed a mass spectrometry (MS)-based immunopeptidomic strategy to characterize HIV-1 peptides presented by a protective allele, HLA-C*12:02. We identified a total of 10,799 unique 8-12-mer peptides, including 15 HIV-1 peptides. The latter included 2 previously-reported immunodominant HIV-1 epitopes; and analysis of T cell responses to the other HIV-1 peptides detected revealed an additional immunodominant epitope. These findings illustrate the utility of MS-based approaches for epitope definition, and emphasize the capacity of HLA-C to present immunodominant T cell epitopes in HIV-infected individuals, indicating the importance of further evaluation of HLA-C-restricted responses to identify novel targets for HIV-1 prophylactic and therapeutic strategies.</jats:p> <jats:p><jats:bold>IMPORTANCE</jats:bold> Mass spectrometry (MS)-based approaches are increasingly being employed for large-scale identification of HLA-bound peptides derived from pathogens, but only very limited profiling of the HIV-1 immunopeptidome has been conducted to date. Notably, a growing body of evidence has recently begun to indicate a protective role for HLA-C in HIV-1 infection, which may suggest that despite the fact that levels of HLA-C expression on both uninfected and HIV-1-infected cells are lower than those of HLA-A/B, HLA-C still presents epitopes to CD8<jats:sup>+</jats:sup> T cells effectively. To explore this, we analyzed HLA-C*12:02-restricted HIV-1 peptides presented on HIV-1-infected cells expressing only HLA-C*12:02 (a protective allele) using LC-MS/MS. We identified a number of novel HLA-C*12:02-bound HIV-1 peptides, and showed that although the majority of them did not elicit T cell responses during natural infection in a Japanese cohort, they included three immunodominant epitopes, emphasizing the contribution of HLA-C to epitope presentation on HIV-infected cells.</jats:p> |
| spellingShingle | Chikata, T Paes, W Akahoshi, T Partridge, T Murakoshi, H Gatanaga, H Ternette, N Oka, S Borrow, P Takiguchi, M Identification of immunodominant HIV-1 epitopes presented by 2 HLA-C*12:02, a protective allele, using an immunopeptidomics 3 approach |
| title | Identification of immunodominant HIV-1 epitopes presented by 2 HLA-C*12:02, a protective allele, using an immunopeptidomics 3 approach |
| title_full | Identification of immunodominant HIV-1 epitopes presented by 2 HLA-C*12:02, a protective allele, using an immunopeptidomics 3 approach |
| title_fullStr | Identification of immunodominant HIV-1 epitopes presented by 2 HLA-C*12:02, a protective allele, using an immunopeptidomics 3 approach |
| title_full_unstemmed | Identification of immunodominant HIV-1 epitopes presented by 2 HLA-C*12:02, a protective allele, using an immunopeptidomics 3 approach |
| title_short | Identification of immunodominant HIV-1 epitopes presented by 2 HLA-C*12:02, a protective allele, using an immunopeptidomics 3 approach |
| title_sort | identification of immunodominant hiv 1 epitopes presented by 2 hla c 12 02 a protective allele using an immunopeptidomics 3 approach |
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