Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses

Stephanie Gras, Lukasz Kedzierski, Sophie A Valkenburg, Karen L Laurie, Yu Chih Liu, Justin T Denholm, Michael J Richards, Guus F Rimmelzwaan, Anne Kelso, Peter C Doherty, Stephen J Turner, Jamie Rossjohn, Katherine Kedzierska

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Preexisting T-cell immunity directed at conserved viral regions promotes enhanced recovery from influenza virus infections, with there being some evidence of cross-protection directed at variable peptides. Strikingly, many of the immunogenic peptides derived from the current pandemic A(H1N1)-2009 influenza virus are representative of the catastrophic 1918 Spanish flu rather than more recent seasonal strains. We present immunological and structural analyses of cross-reactive CD8(+) T-cell-mediated immunity directed at a variable (although highly cross-reactive) immunodominant NP(418-426) peptide that binds to a large B7 family (HLA-B*3501/03/0702) found throughout human populations. Memory CD8(+) T-cell specificity was probed for 12 different NP(418) mutants that emerged over the 9 decades between the 1918 and 2009 pandemics. Although there is evidence of substantial cross-reactivity among seasonal NP(418) mutants, current memory T-cell profiles show no preexisting immunity to the 2009-NP(418) variant or the 1918-NP(418) variant. Natural infection with the A(H1N1)-2009 virus, however, elicits CD8(+) T cells specific for the 2009-NP(418) and 1918-NP(418) epitopes. This analysis points to the potential importance of cross-reactive T-cell populations that cover the possible spectrum of T-cell variants and suggests that the identification of key residues/motifs that elicit cross-reactive T-cell sets could facilitate the evolution of immunization protocols that provide a measure of protection against unpredicted pandemic influenza viruses. Thus, it is worth exploring the potential of vaccines that incorporate peptide variants with a proven potential for broader immunogenicity, especially to those that are not recognized by the current memory T-cell pool generated by exposure to influenza variants that cause successive seasonal epidemics.
Original languageEnglish
Pages (from-to)12599 - 12604
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume107
Issue number28
DOIs
Publication statusPublished - 2010

Cite this

Gras, S., Kedzierski, L., Valkenburg, S. A., Laurie, K. L., Liu, Y. C., Denholm, J. T., ... Kedzierska, K. (2010). Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses. Proceedings of the National Academy of Sciences, 107(28), 12599 - 12604. https://doi.org/10.1073/pnas.1007270107
Gras, Stephanie ; Kedzierski, Lukasz ; Valkenburg, Sophie A ; Laurie, Karen L ; Liu, Yu Chih ; Denholm, Justin T ; Richards, Michael J ; Rimmelzwaan, Guus F ; Kelso, Anne ; Doherty, Peter C ; Turner, Stephen J ; Rossjohn, Jamie ; Kedzierska, Katherine. / Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses. In: Proceedings of the National Academy of Sciences. 2010 ; Vol. 107, No. 28. pp. 12599 - 12604.
@article{2348014b81b942fa88ca885305cc519a,
title = "Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses",
abstract = "Preexisting T-cell immunity directed at conserved viral regions promotes enhanced recovery from influenza virus infections, with there being some evidence of cross-protection directed at variable peptides. Strikingly, many of the immunogenic peptides derived from the current pandemic A(H1N1)-2009 influenza virus are representative of the catastrophic 1918 Spanish flu rather than more recent seasonal strains. We present immunological and structural analyses of cross-reactive CD8(+) T-cell-mediated immunity directed at a variable (although highly cross-reactive) immunodominant NP(418-426) peptide that binds to a large B7 family (HLA-B*3501/03/0702) found throughout human populations. Memory CD8(+) T-cell specificity was probed for 12 different NP(418) mutants that emerged over the 9 decades between the 1918 and 2009 pandemics. Although there is evidence of substantial cross-reactivity among seasonal NP(418) mutants, current memory T-cell profiles show no preexisting immunity to the 2009-NP(418) variant or the 1918-NP(418) variant. Natural infection with the A(H1N1)-2009 virus, however, elicits CD8(+) T cells specific for the 2009-NP(418) and 1918-NP(418) epitopes. This analysis points to the potential importance of cross-reactive T-cell populations that cover the possible spectrum of T-cell variants and suggests that the identification of key residues/motifs that elicit cross-reactive T-cell sets could facilitate the evolution of immunization protocols that provide a measure of protection against unpredicted pandemic influenza viruses. Thus, it is worth exploring the potential of vaccines that incorporate peptide variants with a proven potential for broader immunogenicity, especially to those that are not recognized by the current memory T-cell pool generated by exposure to influenza variants that cause successive seasonal epidemics.",
author = "Stephanie Gras and Lukasz Kedzierski and Valkenburg, {Sophie A} and Laurie, {Karen L} and Liu, {Yu Chih} and Denholm, {Justin T} and Richards, {Michael J} and Rimmelzwaan, {Guus F} and Anne Kelso and Doherty, {Peter C} and Turner, {Stephen J} and Jamie Rossjohn and Katherine Kedzierska",
year = "2010",
doi = "10.1073/pnas.1007270107",
language = "English",
volume = "107",
pages = "12599 -- 12604",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
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Gras, S, Kedzierski, L, Valkenburg, SA, Laurie, KL, Liu, YC, Denholm, JT, Richards, MJ, Rimmelzwaan, GF, Kelso, A, Doherty, PC, Turner, SJ, Rossjohn, J & Kedzierska, K 2010, 'Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses' Proceedings of the National Academy of Sciences, vol. 107, no. 28, pp. 12599 - 12604. https://doi.org/10.1073/pnas.1007270107

Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses. / Gras, Stephanie; Kedzierski, Lukasz; Valkenburg, Sophie A; Laurie, Karen L; Liu, Yu Chih; Denholm, Justin T; Richards, Michael J; Rimmelzwaan, Guus F; Kelso, Anne; Doherty, Peter C; Turner, Stephen J; Rossjohn, Jamie; Kedzierska, Katherine.

In: Proceedings of the National Academy of Sciences, Vol. 107, No. 28, 2010, p. 12599 - 12604.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses

AU - Gras, Stephanie

AU - Kedzierski, Lukasz

AU - Valkenburg, Sophie A

AU - Laurie, Karen L

AU - Liu, Yu Chih

AU - Denholm, Justin T

AU - Richards, Michael J

AU - Rimmelzwaan, Guus F

AU - Kelso, Anne

AU - Doherty, Peter C

AU - Turner, Stephen J

AU - Rossjohn, Jamie

AU - Kedzierska, Katherine

PY - 2010

Y1 - 2010

N2 - Preexisting T-cell immunity directed at conserved viral regions promotes enhanced recovery from influenza virus infections, with there being some evidence of cross-protection directed at variable peptides. Strikingly, many of the immunogenic peptides derived from the current pandemic A(H1N1)-2009 influenza virus are representative of the catastrophic 1918 Spanish flu rather than more recent seasonal strains. We present immunological and structural analyses of cross-reactive CD8(+) T-cell-mediated immunity directed at a variable (although highly cross-reactive) immunodominant NP(418-426) peptide that binds to a large B7 family (HLA-B*3501/03/0702) found throughout human populations. Memory CD8(+) T-cell specificity was probed for 12 different NP(418) mutants that emerged over the 9 decades between the 1918 and 2009 pandemics. Although there is evidence of substantial cross-reactivity among seasonal NP(418) mutants, current memory T-cell profiles show no preexisting immunity to the 2009-NP(418) variant or the 1918-NP(418) variant. Natural infection with the A(H1N1)-2009 virus, however, elicits CD8(+) T cells specific for the 2009-NP(418) and 1918-NP(418) epitopes. This analysis points to the potential importance of cross-reactive T-cell populations that cover the possible spectrum of T-cell variants and suggests that the identification of key residues/motifs that elicit cross-reactive T-cell sets could facilitate the evolution of immunization protocols that provide a measure of protection against unpredicted pandemic influenza viruses. Thus, it is worth exploring the potential of vaccines that incorporate peptide variants with a proven potential for broader immunogenicity, especially to those that are not recognized by the current memory T-cell pool generated by exposure to influenza variants that cause successive seasonal epidemics.

AB - Preexisting T-cell immunity directed at conserved viral regions promotes enhanced recovery from influenza virus infections, with there being some evidence of cross-protection directed at variable peptides. Strikingly, many of the immunogenic peptides derived from the current pandemic A(H1N1)-2009 influenza virus are representative of the catastrophic 1918 Spanish flu rather than more recent seasonal strains. We present immunological and structural analyses of cross-reactive CD8(+) T-cell-mediated immunity directed at a variable (although highly cross-reactive) immunodominant NP(418-426) peptide that binds to a large B7 family (HLA-B*3501/03/0702) found throughout human populations. Memory CD8(+) T-cell specificity was probed for 12 different NP(418) mutants that emerged over the 9 decades between the 1918 and 2009 pandemics. Although there is evidence of substantial cross-reactivity among seasonal NP(418) mutants, current memory T-cell profiles show no preexisting immunity to the 2009-NP(418) variant or the 1918-NP(418) variant. Natural infection with the A(H1N1)-2009 virus, however, elicits CD8(+) T cells specific for the 2009-NP(418) and 1918-NP(418) epitopes. This analysis points to the potential importance of cross-reactive T-cell populations that cover the possible spectrum of T-cell variants and suggests that the identification of key residues/motifs that elicit cross-reactive T-cell sets could facilitate the evolution of immunization protocols that provide a measure of protection against unpredicted pandemic influenza viruses. Thus, it is worth exploring the potential of vaccines that incorporate peptide variants with a proven potential for broader immunogenicity, especially to those that are not recognized by the current memory T-cell pool generated by exposure to influenza variants that cause successive seasonal epidemics.

UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20616031

U2 - 10.1073/pnas.1007270107

DO - 10.1073/pnas.1007270107

M3 - Article

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EP - 12604

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

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ER -