3LKR

Crystal Structure of HLA B*3501 in complex with influenza NP418 epitope from 2009 H1N1 swine origin strain

Summary for 3LKR

• Entry DOI: 10.2210/pdb3lkr/pdb
• Related: 3LKN 3LKO 3LKP 3LKQ 3LKS
• Descriptor: HLA class I histocompatibility antigen, B-35 alpha chain, Beta-2-microglobulin, NP418 epitope from 2009 swine-influenza strain, ... (4 entities in total)
• Functional Keywords: hla b*3501, np418 epitope, influenza, swine-flu, t cell immunity, disulfide bond, glycoprotein, host-virus interaction, immune response, membrane, mhc i, transmembrane, amyloid, amyloidosis, disease mutation, glycation, immunoglobulin domain, pyrrolidone carboxylic acid, secreted, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P30685; Secreted: P61769
• Total number of polymer chains: 3
• Total formula weight: 44883.88

Authors

Gras, S.,Kedzierski, L.,Valkenburg, S.A.,Liu, Y.C.,Denholm, J.,Richards, M.,Rimmelzwaan, G.F.,Doherty, P.C.,Turner, S.J.,Rossjohn, J.,Kedzierska, K. (deposition date: 2010-01-27, release date: 2010-07-07, Last modification date: 2024-10-30)

Primary citation

Gras, S.,Kedzierski, L.,Valkenburg, S.A.,Laurie, K.,Liu, Y.C.,Denholm, J.T.,Richards, M.J.,Rimmelzwaan, G.F.,Kelso, A.,Doherty, P.C.,Turner, S.J.,Rossjohn, J.,Kedzierska, K.
Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses.
Proc.Natl.Acad.Sci.USA, 107:12599-12604, 2010

PubMed 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.

PubMed: 20616031
DOI: 10.1073/pnas.1007270107

Experimental method

X-RAY DIFFRACTION (2 Å)