Giuseppe
Emeritus
Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses (Proc Natl Acad Sci USA, abstract, edited)
[Source: PNAS, original abstract and full text at <cite cite="http://www.pnas.org/content/107/28/12599.short?rss=1">Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses ? PNAS</cite>.]
Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses
1. Stephanie Gras a,1, 2. Lukasz Kedzierski a,b,1, 3. Sophie A. Valkenburg b,1, 4. Karen Laurie c, 5. Yu Chih Liu a, 6. Justin T. Denholm d, 7. Michael J. Richards d, 8. Guus F. Rimmelzwaan e, 9. Anne Kelso c, 10. Peter C. Doherty b,f,2, 11. Stephen J. Turner b, 12. Jamie Rossjohn a,2,3, and 13. Katherine Kedzierska b,2,3
Author Affiliations
1. a Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia;
2. b Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia;
3. c World Health Organization Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria 3051, Australia;
4. d Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, Victoria 3010, Australia;
5. e Department of Virology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; and
6. f Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105
1. ↵1S.G., L.K., and S.A.V. contributed equally to this work.
2. ↵3J.R. and K.K. contributed equally to this work.
3. Contributed by Peter C. Doherty, May 26, 2010 (sent for review April 30, 2010)
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 NP418?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 NP418 mutants that emerged over the 9 decades between the 1918 and 2009 pandemics. Although there is evidence of substantial cross-reactivity among seasonal NP418 mutants, current memory T-cell profiles show no preexisting immunity to the 2009-NP418 variant or the 1918-NP418 variant. Natural infection with the A(H1N1)-2009 virus, however, elicits CD8+ T cells specific for the 2009-NP418 and 1918-NP418 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.
* influenza infection
* T-cell responses
* B7 allelic family
* NP418-426 variants
Footnotes
* 2 To whom correspondence may be addressed. E-mail: pcd@unimelb.unimelb.edu.au, kkedz@unimelb.edu.au, or jamie.rossjohn@med.monash.edu.au.
* Author contributions: S.G., L.K., S.A.V., K.L., J.T.D., M.J.R., G.F.R., A.K., P.C.D., S.J.T., J.R., and K.K. designed research; S.G., L.K., S.A.V., K.L., Y.C.L., and K.K. performed research; S.G., J.T.D., M.J.R., G.F.R., and J.R. contributed new reagents/analytic tools; S.G., L.K., S.A.V., K.L., J.R., and K.K. analyzed data; and S.G., L.K., S.A.V., J.T.D., G.F.R., A.K., P.C.D., S.J.T., J.R., and K.K. wrote the paper.
* The authors declare no conflict of interest.
* Data deposition: The atomic coordinates and structure factors of the HLA-B*3501-NP418 complexes have been deposited in the Protein Data Bank as follows: NP-2009 (PDB ID code 3LKR), NP-1980 (PDB ID code 3LKR), NP-1977 (PDB ID code 3LKQ), NP-1972 (PDB ID code 3LKP), NP-1934 (PDB ID code 3LKO), and NP-1918 (PDB ID code 3LKN).
* This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1007270107/-/DCSupplemental.
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[Source: PNAS, original abstract and full text at <cite cite="http://www.pnas.org/content/107/28/12599.short?rss=1">Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses ? PNAS</cite>.]
Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses
1. Stephanie Gras a,1, 2. Lukasz Kedzierski a,b,1, 3. Sophie A. Valkenburg b,1, 4. Karen Laurie c, 5. Yu Chih Liu a, 6. Justin T. Denholm d, 7. Michael J. Richards d, 8. Guus F. Rimmelzwaan e, 9. Anne Kelso c, 10. Peter C. Doherty b,f,2, 11. Stephen J. Turner b, 12. Jamie Rossjohn a,2,3, and 13. Katherine Kedzierska b,2,3
Author Affiliations
1. a Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia;
2. b Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia;
3. c World Health Organization Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria 3051, Australia;
4. d Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, Victoria 3010, Australia;
5. e Department of Virology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; and
6. f Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105
1. ↵1S.G., L.K., and S.A.V. contributed equally to this work.
2. ↵3J.R. and K.K. contributed equally to this work.
3. Contributed by Peter C. Doherty, May 26, 2010 (sent for review April 30, 2010)
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 NP418?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 NP418 mutants that emerged over the 9 decades between the 1918 and 2009 pandemics. Although there is evidence of substantial cross-reactivity among seasonal NP418 mutants, current memory T-cell profiles show no preexisting immunity to the 2009-NP418 variant or the 1918-NP418 variant. Natural infection with the A(H1N1)-2009 virus, however, elicits CD8+ T cells specific for the 2009-NP418 and 1918-NP418 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.
* influenza infection
* T-cell responses
* B7 allelic family
* NP418-426 variants
Footnotes
* 2 To whom correspondence may be addressed. E-mail: pcd@unimelb.unimelb.edu.au, kkedz@unimelb.edu.au, or jamie.rossjohn@med.monash.edu.au.
* Author contributions: S.G., L.K., S.A.V., K.L., J.T.D., M.J.R., G.F.R., A.K., P.C.D., S.J.T., J.R., and K.K. designed research; S.G., L.K., S.A.V., K.L., Y.C.L., and K.K. performed research; S.G., J.T.D., M.J.R., G.F.R., and J.R. contributed new reagents/analytic tools; S.G., L.K., S.A.V., K.L., J.R., and K.K. analyzed data; and S.G., L.K., S.A.V., J.T.D., G.F.R., A.K., P.C.D., S.J.T., J.R., and K.K. wrote the paper.
* The authors declare no conflict of interest.
* Data deposition: The atomic coordinates and structure factors of the HLA-B*3501-NP418 complexes have been deposited in the Protein Data Bank as follows: NP-2009 (PDB ID code 3LKR), NP-1980 (PDB ID code 3LKR), NP-1977 (PDB ID code 3LKQ), NP-1972 (PDB ID code 3LKP), NP-1934 (PDB ID code 3LKO), and NP-1918 (PDB ID code 3LKN).
* This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1007270107/-/DCSupplemental.
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