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http://purl.uniprot.org/citations/24990997http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24990997http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24990997http://www.w3.org/2000/01/rdf-schema#comment"

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Cytotoxic T lymphocytes recognizing conserved peptide epitopes are crucial for protection against influenza A virus (IAV) infection. The CD8 T cell response against the M158-66 (GILGFVFTL) matrix protein epitope is immunodominant when restricted by HLA-A*02, a major histocompatibility complex (MHC) molecule expressed by approximately half of the human population. Here we report that the GILGFVFTL peptide is restricted by multiple HLA-C*08 alleles as well. We observed that M158-66 was able to elicit cytotoxic T lymphocyte (CTL) responses in both HLA-A*02- and HLA-C*08-positive individuals and that GILGFVFTL-specific CTLs in individuals expressing both restriction elements were distinct and not cross-reactive. The crystal structure of GILGFVFTL-HLA-C*08:01 was solved at 1.84 Å, and comparison with the known GILGFVFTL-HLA-A*02:01 structure revealed that the antigen bound both complexes in near-identical conformations, accommodated by binding pockets shaped from shared as well as unique residues. This discovery of degenerate peptide presentation by both HLA-A and HLA-C allelic variants eliciting unique CTL responses to IAV infection contributes fundamental knowledge with important implications for vaccine development strategies.

Importance

The presentation of influenza A virus peptides to elicit immunity is thought to be narrowly restricted, with a single peptide presented by a specific HLA molecule. In this study, we show that the same influenza A virus peptide can be more broadly presented by both HLA-A and HLA-C molecules. This discovery may help to explain the differences in immunity to influenza A virus between individuals and populations and may also aid in the design of vaccines."xsd:string
http://purl.uniprot.org/citations/24990997http://purl.org/dc/terms/identifier"doi:10.1128/jvi.00855-14"xsd:string
http://purl.uniprot.org/citations/24990997http://purl.org/dc/terms/identifier"doi:10.1128/jvi.00855-14"xsd:string
http://purl.uniprot.org/citations/24990997http://purl.org/dc/terms/identifier"doi:10.1128/JVI.00855-14"xsd:string
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/author"Liu J."xsd:string
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/author"Liu J."xsd:string
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/author"Ren E.C."xsd:string
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/author"Ren E.C."xsd:string
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/author"Choo J.A."xsd:string
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/author"Choo J.A."xsd:string
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/author"Grotenbreg G.M."xsd:string
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/author"Grotenbreg G.M."xsd:string
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/author"Toh X."xsd:string
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/author"Toh X."xsd:string
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/name"J. Virol."xsd:string
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/name"J. Virol."xsd:string
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/pages"10613-10623"xsd:string
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/pages"10613-10623"xsd:string
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/title"The immunodominant influenza A virus M158-66 cytotoxic T lymphocyte epitope exhibits degenerate class I major histocompatibility complex restriction in humans."xsd:string
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/title"The immunodominant influenza A virus M158-66 cytotoxic T lymphocyte epitope exhibits degenerate class I major histocompatibility complex restriction in humans."xsd:string
http://purl.uniprot.org/citations/24990997http://purl.uniprot.org/core/volume"88"xsd:string
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