HIV-1 epitopes presented by MHC class I types associated with superior immune containment of viremia have highly constrained fitness landscapes.
Certain Major Histocompatibility-I (MHC-I) types are associated with superior immune containment of HIV-1 infection by CD8+ cytotoxic T lymphocytes (CTLs), but the mechanisms mediating this containment are difficult to elucidate in vivo. Here we provide controlled assessments of fitness landscapes a...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-08-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1006541&type=printable |
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| author | Aleksandr M Gorin Yushen Du Franklin Y Liu Tian-Hao Zhang Hwee L Ng Christian Hofmann William G Cumberland Ren Sun Otto O Yang |
| author_facet | Aleksandr M Gorin Yushen Du Franklin Y Liu Tian-Hao Zhang Hwee L Ng Christian Hofmann William G Cumberland Ren Sun Otto O Yang |
| author_sort | Aleksandr M Gorin |
| collection | DOAJ |
| description | Certain Major Histocompatibility-I (MHC-I) types are associated with superior immune containment of HIV-1 infection by CD8+ cytotoxic T lymphocytes (CTLs), but the mechanisms mediating this containment are difficult to elucidate in vivo. Here we provide controlled assessments of fitness landscapes and CTL-imposed constraints for immunodominant epitopes presented by two protective (B*57 and B*27) and one non-protective (A*02) MHC-I types. Libraries of HIV-1 with saturation mutagenesis of CTL epitopes are propagated with and without CTL selective pressure to define the fitness landscapes for epitope mutation and escape from CTLs via deep sequencing. Immunodominant B*57- and B*27- present epitopes are highly limited in options for fit mutations, with most viable variants recognizable by CTLs, whereas an immunodominant A*02 epitope-presented is highly permissive for mutation, with many options for CTL evasion without loss of viability. Generally, options for evasion overlap considerably between CTL clones despite highly distinct T cell receptors. Finally, patterns of variant recognition suggest population-wide CTL selection for the A*02-presented epitope. Overall, these findings indicate that these protective MHC-I types yield CTL targeting of highly constrained epitopes, and underscore the importance of blocking public escape pathways for CTL-based interventions against HIV-1. |
| format | Article |
| id | doaj-art-d0010ea8075a45f3a2e7cfcf3ab01e0d |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2017-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-d0010ea8075a45f3a2e7cfcf3ab01e0d2025-08-20T02:45:28ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742017-08-01138e100654110.1371/journal.ppat.1006541HIV-1 epitopes presented by MHC class I types associated with superior immune containment of viremia have highly constrained fitness landscapes.Aleksandr M GorinYushen DuFranklin Y LiuTian-Hao ZhangHwee L NgChristian HofmannWilliam G CumberlandRen SunOtto O YangCertain Major Histocompatibility-I (MHC-I) types are associated with superior immune containment of HIV-1 infection by CD8+ cytotoxic T lymphocytes (CTLs), but the mechanisms mediating this containment are difficult to elucidate in vivo. Here we provide controlled assessments of fitness landscapes and CTL-imposed constraints for immunodominant epitopes presented by two protective (B*57 and B*27) and one non-protective (A*02) MHC-I types. Libraries of HIV-1 with saturation mutagenesis of CTL epitopes are propagated with and without CTL selective pressure to define the fitness landscapes for epitope mutation and escape from CTLs via deep sequencing. Immunodominant B*57- and B*27- present epitopes are highly limited in options for fit mutations, with most viable variants recognizable by CTLs, whereas an immunodominant A*02 epitope-presented is highly permissive for mutation, with many options for CTL evasion without loss of viability. Generally, options for evasion overlap considerably between CTL clones despite highly distinct T cell receptors. Finally, patterns of variant recognition suggest population-wide CTL selection for the A*02-presented epitope. Overall, these findings indicate that these protective MHC-I types yield CTL targeting of highly constrained epitopes, and underscore the importance of blocking public escape pathways for CTL-based interventions against HIV-1.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1006541&type=printable |
| spellingShingle | Aleksandr M Gorin Yushen Du Franklin Y Liu Tian-Hao Zhang Hwee L Ng Christian Hofmann William G Cumberland Ren Sun Otto O Yang HIV-1 epitopes presented by MHC class I types associated with superior immune containment of viremia have highly constrained fitness landscapes. PLoS Pathogens |
| title | HIV-1 epitopes presented by MHC class I types associated with superior immune containment of viremia have highly constrained fitness landscapes. |
| title_full | HIV-1 epitopes presented by MHC class I types associated with superior immune containment of viremia have highly constrained fitness landscapes. |
| title_fullStr | HIV-1 epitopes presented by MHC class I types associated with superior immune containment of viremia have highly constrained fitness landscapes. |
| title_full_unstemmed | HIV-1 epitopes presented by MHC class I types associated with superior immune containment of viremia have highly constrained fitness landscapes. |
| title_short | HIV-1 epitopes presented by MHC class I types associated with superior immune containment of viremia have highly constrained fitness landscapes. |
| title_sort | hiv 1 epitopes presented by mhc class i types associated with superior immune containment of viremia have highly constrained fitness landscapes |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1006541&type=printable |
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