tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A. 2010 Jun 28. [Epub ahead of print]
Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses.
Gras S, Kedzierski L, Valkenburg SA, Laurie K, Liu YC, Denholm JT, Richards MJ, Rimmelzwaan GF, Kelso A, Doherty PC, Turner SJ, Rossjohn J, Kedzierska K.
Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
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.
PMID: 20616031 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20616031
Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses.
Gras S, Kedzierski L, Valkenburg SA, Laurie K, Liu YC, Denholm JT, Richards MJ, Rimmelzwaan GF, Kelso A, Doherty PC, Turner SJ, Rossjohn J, Kedzierska K.
Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
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.
PMID: 20616031 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20616031