4L8C

Crystal structure of the H2Db in complex with the NP-N3D peptide

Summary for 4L8C

• Entry DOI: 10.2210/pdb4l8c/pdb
• Related: 4HUU 4HUV 4HUW 4HUX 4HV8 4L8B 4L8D
• Descriptor: H-2 class I histocompatibility antigen, D-B alpha chain, Beta-2-microglobulin, NP-N3D peptide, ... (5 entities in total)
• Functional Keywords: influenza, viral escape, t cell immunity, immune system
• Biological source: Mus musculus (mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01899; Secreted: P01887
• Total number of polymer chains: 12
• Total formula weight: 181110.50

Authors

Rossjohn, J.,Gras, S. (deposition date: 2013-06-16, release date: 2013-10-16, Last modification date: 2024-10-30)

Primary citation

Valkenburg, S.A.,Quinones-Parra, S.,Gras, S.,Komadina, N.,McVernon, J.,Wang, Z.,Halim, H.,Iannello, P.,Cole, C.,Laurie, K.,Kelso, A.,Rossjohn, J.,Doherty, P.C.,Turner, S.J.,Kedzierska, K.
Acute emergence and reversion of influenza A virus quasispecies within CD8(+) T cell antigenic peptides.
Nat Commun, 4:2663-2663, 2013

PubMed Abstract: Influenza A virus-specific CD8(+) cytotoxic T lymphocytes (CTLs) provide a degree of cross-strain protection that is potentially subverted by mutation. Here we describe the sequential emergence of such variants within CTL epitopes for a persistently infected, immunocompromised infant. Further analysis in immunodeficient and wild-type mice supports the view that CTL escape variants arise frequently in influenza, accumulate with time and revert in the absence of immune pressure under MHCI-mismatched conditions. Viral fitness, the abundance of endogenous CD8(+) T cell responses and T cell receptor repertoire diversity influence the nature of these de novo mutants. Structural characterization of dominant escape variants shows how the peptide-MHCI interaction is modified to affect variant-MHCI stability. The mechanism of influenza virus escape thus looks comparable to that recognized for chronic RNA viruses like HIV and HCV, suggesting that immunocompromised patients with prolonged viral infection could have an important part in the emergence of influenza quasispecies.

PubMed: 24173108
DOI: 10.1038/ncomms3663

Experimental method

X-RAY DIFFRACTION (2.8 Å)