2011
DOI: 10.1073/pnas.1105624108
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Systematic identification of immunodominant CD8+T-cell responses to influenza A virus in HLA-A2 individuals

Abstract: Immunodominant T-cell responses are important for virus clearance. However, the identification of immunodominant T-cell peptide + HLA glycoprotein epitopes has been hindered by the extent of HLA polymorphism and the limitations of predictive algorithms. A simple, systematic approach has been used here to screen for immunodominant CD8 + T-cell specificities. The analysis targeted healthy HLA-A2 + donors to allow comparison with responses to the well-studied influe… Show more

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Cited by 78 publications
(105 citation statements)
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“…In these mice, the majority of CD8 + T cells produced in response to influenza virus infection of the respiratory tract recognize only 1 octamer of viral origin (NP 366-374 in association with D b ) of the over 4,000 potential octamers in the virus's proteome (about 4,400-aa residues encoded in 11 proteins). Similar immunodominance of a few peptides is also evident in humans infected with influenza virus, but the dominant peptides differ among various individuals, even those individuals sharing the same restricting MHC (36). Altering the route of vaccinia virus infection in mice also results in changes in the vaccinia virus-derived dominant peptides that elicit T-cell responses (37,38).…”
Section: Discussionmentioning
confidence: 80%
“…In these mice, the majority of CD8 + T cells produced in response to influenza virus infection of the respiratory tract recognize only 1 octamer of viral origin (NP 366-374 in association with D b ) of the over 4,000 potential octamers in the virus's proteome (about 4,400-aa residues encoded in 11 proteins). Similar immunodominance of a few peptides is also evident in humans infected with influenza virus, but the dominant peptides differ among various individuals, even those individuals sharing the same restricting MHC (36). Altering the route of vaccinia virus infection in mice also results in changes in the vaccinia virus-derived dominant peptides that elicit T-cell responses (37,38).…”
Section: Discussionmentioning
confidence: 80%
“…However, the immunodominant epitopes were quite different between individuals with different HLA alleles (7,8). On the other hand, 774 human CD4 ϩ T cell epitopes for IAV are currently indexed in the IEDB, three times the number of indexed CD8 ϩ T cell epitopes; 51% of these are shown as derived from HA, 15% from NP, 13% from M1, and 11% from NA.…”
Section: Munodominant Cd8mentioning
confidence: 99%
“…We previously developed a systematic protocol for identifying immunodominant CD8 ϩ T cell responses by using in vitro expanded-multispecificity IAV-specific T cell lines, rVVs encoding 11 individual IAV proteins, and synthetic overlapping peptides (7,8). Based on that protocol, we developed a similar approach for identifying immunodominant CD4…”
Section: Identification Of Immunodominant Cd4mentioning
confidence: 99%
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