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- Publisher Website: 10.1073/pnas.1603106113
- Scopus: eid_2-s2.0-84964331011
- PMID: 27036003
- WOS: WOS:000374393800059
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Article: Molecular basis for universal HLA-A*0201–restricted CD8+ T-cell immunity against influenza viruses
Title | Molecular basis for universal HLA-A*0201–restricted CD8+ T-cell immunity against influenza viruses |
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Authors | |
Keywords | Human CD8+ T cells Influenza infection T-cell receptor |
Issue Date | 2016 |
Citation | Proceedings of the National Academy of Sciences of the United States of America, 2016, v. 113, n. 16, p. 4440-4445 How to Cite? |
Abstract | Memory CD8+ T lymphocytes (CTLs) specific for antigenic peptides derived from internal viral proteins confer broad protection against distinct strains of influenza A virus (IAV). However, immune efficacy can be undermined by the emergence of escape mutants. To determine how T-cell receptor (TCR) composition relates to IAV epitope variability, we used ex vivo peptide-HLA tetramer enrichment and single-cell multiplex analysis to compare TCRs targeted to the largely conserved HLA-A∗0201-M158 and the hypervariable HLA-B∗3501-NP418 antigens. The TCRαβs for HLA-B∗3501-NP418+ CTLs varied among individuals and across IAV strains, indicating that a range of mutated peptides will prime different NP418-specific CTL sets. Conversely, a dominant public TRAV27/TRBV19+ TCRαβ was selected in HLA-A∗0201+ donors responding to M158. This public TCR cross-recognized naturally occurring M158 variants complexed with HLA-A∗0201. Ternary structures showed that induced-fit molecular mimicry underpins TRAV27/TRBV19+ TCR specificity for the WT and mutant M158 peptides, suggesting the possibility of universal CTL immunity in HLA-A∗0201+ individuals. Combined with the high population frequency of HLA-A∗0201, these data potentially explain the relative conservation of M158. Moreover, our results suggest that vaccination strategies aimed at generating broad protection should incorporate variant peptides to elicit cross-reactive responses against other specificities, especially those that may be relatively infrequent among IAV-primed memory CTLs. |
Persistent Identifier | http://hdl.handle.net/10722/241222 |
ISSN | 2023 Impact Factor: 9.4 2023 SCImago Journal Rankings: 3.737 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Valkenburg, Sophie A. | - |
dc.contributor.author | Josephs, Tracy M. | - |
dc.contributor.author | Clemens, E. Bridie | - |
dc.contributor.author | Grant, Emma J. | - |
dc.contributor.author | Nguyen, Thi H.O. | - |
dc.contributor.author | Wang, George C. | - |
dc.contributor.author | Price, David A. | - |
dc.contributor.author | Miller, Adrian | - |
dc.contributor.author | Tong, Steven Y.C. | - |
dc.contributor.author | Thomas, Paul G. | - |
dc.contributor.author | Doherty, Peter C. | - |
dc.contributor.author | Rossjohn, Jamie | - |
dc.contributor.author | Gras, Stephanie | - |
dc.contributor.author | Kedzierska, Katherine | - |
dc.date.accessioned | 2017-05-26T03:37:08Z | - |
dc.date.available | 2017-05-26T03:37:08Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | Proceedings of the National Academy of Sciences of the United States of America, 2016, v. 113, n. 16, p. 4440-4445 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/10722/241222 | - |
dc.description.abstract | Memory CD8+ T lymphocytes (CTLs) specific for antigenic peptides derived from internal viral proteins confer broad protection against distinct strains of influenza A virus (IAV). However, immune efficacy can be undermined by the emergence of escape mutants. To determine how T-cell receptor (TCR) composition relates to IAV epitope variability, we used ex vivo peptide-HLA tetramer enrichment and single-cell multiplex analysis to compare TCRs targeted to the largely conserved HLA-A∗0201-M158 and the hypervariable HLA-B∗3501-NP418 antigens. The TCRαβs for HLA-B∗3501-NP418+ CTLs varied among individuals and across IAV strains, indicating that a range of mutated peptides will prime different NP418-specific CTL sets. Conversely, a dominant public TRAV27/TRBV19+ TCRαβ was selected in HLA-A∗0201+ donors responding to M158. This public TCR cross-recognized naturally occurring M158 variants complexed with HLA-A∗0201. Ternary structures showed that induced-fit molecular mimicry underpins TRAV27/TRBV19+ TCR specificity for the WT and mutant M158 peptides, suggesting the possibility of universal CTL immunity in HLA-A∗0201+ individuals. Combined with the high population frequency of HLA-A∗0201, these data potentially explain the relative conservation of M158. Moreover, our results suggest that vaccination strategies aimed at generating broad protection should incorporate variant peptides to elicit cross-reactive responses against other specificities, especially those that may be relatively infrequent among IAV-primed memory CTLs. | - |
dc.language | eng | - |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.subject | Human CD8+ T cells | - |
dc.subject | Influenza infection | - |
dc.subject | T-cell receptor | - |
dc.title | Molecular basis for universal HLA-A*0201–restricted CD8+ T-cell immunity against influenza viruses | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1073/pnas.1603106113 | - |
dc.identifier.pmid | 27036003 | - |
dc.identifier.scopus | eid_2-s2.0-84964331011 | - |
dc.identifier.volume | 113 | - |
dc.identifier.issue | 16 | - |
dc.identifier.spage | 4440 | - |
dc.identifier.epage | 4445 | - |
dc.identifier.eissn | 1091-6490 | - |
dc.identifier.isi | WOS:000374393800059 | - |
dc.identifier.issnl | 0027-8424 | - |