4NT6

HLA-C*0801 Crystal Structure

Summary for 4NT6

• Entry DOI: 10.2210/pdb4nt6/pdb
• Related: 4NT7
• Descriptor: HLA class I histocompatibility antigen, Cw-8 alpha chain, Beta-2-microglobulin, Matrix protein 1, ... (4 entities in total)
• Functional Keywords: class i histocompatibility antigen, hla-c1, hla-c*08, extracellular, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P30505; Secreted: P61769
• Total number of polymer chains: 3
• Total formula weight: 44479.38

Authors

Liu, J.X.,Toh, X.Y.,Ren, E.C. (deposition date: 2013-12-01, release date: 2014-07-23, Last modification date: 2024-10-16)

Primary citation

Choo, J.A.,Liu, J.,Toh, X.,Grotenbreg, G.M.,Ren, E.C.
The immunodominant influenza A virus M158-66 cytotoxic T lymphocyte epitope exhibits degenerate class I major histocompatibility complex restriction in humans.
J.Virol., 88:10613-10623, 2014

PubMed Abstract: Cytotoxic T lymphocytes recognizing conserved peptide epitopes are crucial for protection against influenza A virus (IAV) infection. The CD8 T cell response against the M158-66 (GILGFVFTL) matrix protein epitope is immunodominant when restricted by HLA-A*02, a major histocompatibility complex (MHC) molecule expressed by approximately half of the human population. Here we report that the GILGFVFTL peptide is restricted by multiple HLA-C*08 alleles as well. We observed that M158-66 was able to elicit cytotoxic T lymphocyte (CTL) responses in both HLA-A*02- and HLA-C*08-positive individuals and that GILGFVFTL-specific CTLs in individuals expressing both restriction elements were distinct and not cross-reactive. The crystal structure of GILGFVFTL-HLA-C*08:01 was solved at 1.84 Å, and comparison with the known GILGFVFTL-HLA-A*02:01 structure revealed that the antigen bound both complexes in near-identical conformations, accommodated by binding pockets shaped from shared as well as unique residues. This discovery of degenerate peptide presentation by both HLA-A and HLA-C allelic variants eliciting unique CTL responses to IAV infection contributes fundamental knowledge with important implications for vaccine development strategies.

PubMed: 24990997
DOI: 10.1128/JVI.00855-14

Experimental method

X-RAY DIFFRACTION (1.84 Å)