5HHN: Crystal Structure Of Hla-a*0201 In Complex With M1-f5l

Memory CD8(+)T lymphocytes (CTLs) specific for antigenic peptides derived from internal viral proteins confer broad protection against distinct strains of influenza A virus (IAV). However, immune efficacy can be undermined by the emergence of escape mutants. To determine how T-cell receptor (TCR) composition relates to IAV epitope variability, we used ex vivo peptide-HLA tetramer enrichment and single-cell multiplex analysis to compare TCRs targeted to the largely conserved HLA-A*0201-M158and the hypervariable HLA-B*3501-NP418antigens. The TCRalphabetas for HLA-B*3501-NP418 (+)CTLs varied among individuals and across IAV strains, indicating that a range of mutated peptides will prime different NP418-specific CTL sets. Conversely, a dominant public TRAV27/TRBV19(+)TCRalphabeta was selected in HLA-A*0201(+)donors responding to M158 This public TCR cross-recognized naturally occurring M158variants complexed with HLA-A*0201. Ternary structures showed that induced-fit molecular mimicry underpins TRAV27/TRBV19(+)TCR specificity for the WT and mutant M158peptides, suggesting the possibility of universal CTL immunity in HLA-A*0201(+)individuals. Combined with the high population frequency of HLA-A*0201, these data potentially explain the relative conservation of M158 Moreover, our results suggest that vaccination strategies aimed at generating broad protection should incorporate variant peptides to elicit cross-reactive responses against other specificities, especially those that may be relatively infrequent among IAV-primed memory CTLs.
PDB ID: 5HHNDownload
MMDB ID: 137758
PDB Deposition Date: 2016/1/11
Updated in MMDB: 2016/05
Experimental Method:
x-ray diffraction
Resolution: 2.03  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 5HHN: trimeric; determined by author and by software (PISA)
Molecular Components in 5HHN
Label Count Molecule
Proteins (3 molecules)
HLA Class I Histocompatibility Antigen, A-2 Alpha Chain(Gene symbol: HLA-A)
Molecule annotation
Beta-2-microglobulin(Gene symbol: B2M)
Molecule annotation
M1-f5l, Gilglvftl
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB