Mutational Escape in HIV-1 CTL Epitopes Leads to Increased Binding to Inhibitory Myelomonocytic MHC Class I Receptors
Escape mutations in HIV-1 cytotoxic T cell (CTL) epitopes can abrogate recognition by the TCR of HIV-1-specific CD8+ T cells, but may also change interactions with alternative MHC class I receptors. Here, we show that mutational escape in three HLA-A11-, B8- and B7- restricted immunodominant HIV-1 C...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2011
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| Online Access: | http://hdl.handle.net/1721.1/64947 |
| _version_ | 1826196609375928320 |
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| author | Yang, Yue Huang, Jinghe Toth, Ildiko Lichterfeld, Mathias Yu, Xu G. |
| author2 | Yang, Yue |
| author_facet | Yang, Yue Yang, Yue Huang, Jinghe Toth, Ildiko Lichterfeld, Mathias Yu, Xu G. |
| author_sort | Yang, Yue |
| collection | MIT |
| description | Escape mutations in HIV-1 cytotoxic T cell (CTL) epitopes can abrogate recognition by the TCR of HIV-1-specific CD8+ T cells, but may also change interactions with alternative MHC class I receptors. Here, we show that mutational escape in three HLA-A11-, B8- and B7- restricted immunodominant HIV-1 CTL epitopes consistently enhances binding of the respective peptide/MHC class I complex to Immunoglobulin-like transcript 4 (ILT4), an inhibitory myelomonocytic MHC class I receptor expressed on monocytes and dendritic cells. In contrast, mutational escape in an alternative immunodominant HLA-B57-restricted CTL epitope did not affect ILT4-mediated recognition by myelomonocytic cells. This suggests that in addition to abrogating recognition by HIV-1-specific CD8 T cells, mutational escape in some, but not all CTL epitopes may mediate important immunoregulatory effects by increasing binding properties to ILT4, and augmenting ILT4-mediated inhibitory effects of professional antigen-presenting cells. |
| first_indexed | 2024-09-23T10:30:10Z |
| format | Article |
| id | mit-1721.1/64947 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:30:10Z |
| publishDate | 2011 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/649472022-09-30T21:31:07Z Mutational Escape in HIV-1 CTL Epitopes Leads to Increased Binding to Inhibitory Myelomonocytic MHC Class I Receptors Yang, Yue Huang, Jinghe Toth, Ildiko Lichterfeld, Mathias Yu, Xu G. Yang, Yue Yang, Yue Escape mutations in HIV-1 cytotoxic T cell (CTL) epitopes can abrogate recognition by the TCR of HIV-1-specific CD8+ T cells, but may also change interactions with alternative MHC class I receptors. Here, we show that mutational escape in three HLA-A11-, B8- and B7- restricted immunodominant HIV-1 CTL epitopes consistently enhances binding of the respective peptide/MHC class I complex to Immunoglobulin-like transcript 4 (ILT4), an inhibitory myelomonocytic MHC class I receptor expressed on monocytes and dendritic cells. In contrast, mutational escape in an alternative immunodominant HLA-B57-restricted CTL epitope did not affect ILT4-mediated recognition by myelomonocytic cells. This suggests that in addition to abrogating recognition by HIV-1-specific CD8 T cells, mutational escape in some, but not all CTL epitopes may mediate important immunoregulatory effects by increasing binding properties to ILT4, and augmenting ILT4-mediated inhibitory effects of professional antigen-presenting cells. National Institutes of Health (U.S.) (Grant R01 AI078799) National Institutes of Health (U.S.) (Grant P01 AI074415) Doris Duke Charitable Foundation 2011-07-20T21:05:06Z 2011-07-20T21:05:06Z 2010-12 2010-08 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/64947 Yang, Yue, Huang J, Toth I, Lichterfeld M, Yu XG (2010) Mutational Escape in HIV-1 CTL Epitopes Leads to Increased Binding to Inhibitory Myelomonocytic MHC Class I Receptors. PLoS ONE 5(12): e15084. © 2010 Yang et al. en_US http://dx.doi.org/10.1371/journal.pone.0015084 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Yang, Yue Huang, Jinghe Toth, Ildiko Lichterfeld, Mathias Yu, Xu G. Mutational Escape in HIV-1 CTL Epitopes Leads to Increased Binding to Inhibitory Myelomonocytic MHC Class I Receptors |
| title | Mutational Escape in HIV-1 CTL Epitopes Leads to Increased Binding to Inhibitory Myelomonocytic MHC Class I Receptors |
| title_full | Mutational Escape in HIV-1 CTL Epitopes Leads to Increased Binding to Inhibitory Myelomonocytic MHC Class I Receptors |
| title_fullStr | Mutational Escape in HIV-1 CTL Epitopes Leads to Increased Binding to Inhibitory Myelomonocytic MHC Class I Receptors |
| title_full_unstemmed | Mutational Escape in HIV-1 CTL Epitopes Leads to Increased Binding to Inhibitory Myelomonocytic MHC Class I Receptors |
| title_short | Mutational Escape in HIV-1 CTL Epitopes Leads to Increased Binding to Inhibitory Myelomonocytic MHC Class I Receptors |
| title_sort | mutational escape in hiv 1 ctl epitopes leads to increased binding to inhibitory myelomonocytic mhc class i receptors |
| url | http://hdl.handle.net/1721.1/64947 |
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