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Article: HIV-1 epitopes presented by MHC class I types associated with superior immune containment of viremia have highly constrained fitness landscapes

TitleHIV-1 epitopes presented by MHC class I types associated with superior immune containment of viremia have highly constrained fitness landscapes
Authors
Issue Date2017
Citation
PLoS Pathogens, 2017, v. 13, n. 8, article no. e1006541 How to Cite?
Abstract© 2017 Gorin et al. 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.
Persistent Identifierhttp://hdl.handle.net/10722/285796
ISSN
2023 Impact Factor: 5.5
2023 SCImago Journal Rankings: 2.223
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGorin, Aleksandr M.-
dc.contributor.authorDu, Yushen-
dc.contributor.authorLiu, Franklin Y.-
dc.contributor.authorZhang, Tian Hao-
dc.contributor.authorNg, Hwee L.-
dc.contributor.authorHofmann, Christian-
dc.contributor.authorCumberland, William G.-
dc.contributor.authorSun, Ren-
dc.contributor.authorYang, Otto O.-
dc.date.accessioned2020-08-18T04:56:40Z-
dc.date.available2020-08-18T04:56:40Z-
dc.date.issued2017-
dc.identifier.citationPLoS Pathogens, 2017, v. 13, n. 8, article no. e1006541-
dc.identifier.issn1553-7366-
dc.identifier.urihttp://hdl.handle.net/10722/285796-
dc.description.abstract© 2017 Gorin et al. 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.-
dc.languageeng-
dc.relation.ispartofPLoS Pathogens-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleHIV-1 epitopes presented by MHC class I types associated with superior immune containment of viremia have highly constrained fitness landscapes-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.ppat.1006541-
dc.identifier.pmid28787455-
dc.identifier.pmcidPMC5560751-
dc.identifier.scopuseid_2-s2.0-85028685522-
dc.identifier.volume13-
dc.identifier.issue8-
dc.identifier.spagearticle no. e1006541-
dc.identifier.epagearticle no. e1006541-
dc.identifier.eissn1553-7374-
dc.identifier.isiWOS:000408758400021-
dc.identifier.f1000727964852-
dc.identifier.issnl1553-7366-

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