Show simple item record

dc.contributor.authorValkenburg, Sophie A
dc.contributor.authorJosephs, Tracy M
dc.contributor.authorClemens, E Bridie
dc.contributor.authorGrant, Emma J
dc.contributor.authorNguyen, Thi HO
dc.contributor.authorWang, George C
dc.contributor.authorPrice, David A
dc.contributor.authorMiller, Adrian
dc.contributor.authorTong, Steven YC
dc.contributor.authorThomas, Paul G
dc.contributor.authorDoherty, Peter C
dc.contributor.authorRossjohn, Jamie
dc.contributor.authorGras, Stephanie
dc.contributor.authorKedzierska, Katherine
dc.date.accessioned2018-12-13T01:30:48Z
dc.date.available2018-12-13T01:30:48Z
dc.date.issued2016
dc.identifier.issn0027-8424
dc.identifier.doi10.1073/pnas.1603106113
dc.identifier.urihttp://hdl.handle.net/10072/142554
dc.description.abstractMemory 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.description.peerreviewedYes
dc.languageEnglish
dc.publisherNational Academy of Sciences
dc.relation.ispartofpagefrom4440
dc.relation.ispartofpageto4445
dc.relation.ispartofissue16
dc.relation.ispartofjournalProceedings of the National Academy of Sciences of the United States of America
dc.relation.ispartofvolume113
dc.subject.fieldofresearchImmunology not elsewhere classified
dc.subject.fieldofresearchcode110799
dc.titleMolecular basis for universal HLA-A*0201-restricted CD8+ T-cell immunity against influenza viruses
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorMiller, Adrian


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record