5HHP

Crystal Structure of HLA-A*0201 in complex with M1-G4E

Summary for 5HHP

• Entry DOI: 10.2210/pdb5hhp/pdb
• Related: 5HHM 5HHN 5HHO 5HHQ
• Descriptor: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, M1-G4E, GILEFVFTL, ... (4 entities in total)
• Functional Keywords: hla a*0201, influenza, m1, tcr, t cell, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01892; Secreted : P61769
• Total number of polymer chains: 3
• Total formula weight: 44670.73

Authors

Gras, S.,Josephs, T.M.,Rossjohn, J. (deposition date: 2016-01-11, release date: 2016-03-23, Last modification date: 2024-10-23)

Primary citation

Valkenburg, S.A.,Josephs, T.M.,Clemens, E.B.,Grant, E.J.,Nguyen, T.H.,Wang, G.C.,Price, D.A.,Miller, A.,Tong, S.Y.,Thomas, P.G.,Doherty, P.C.,Rossjohn, J.,Gras, S.,Kedzierska, K.
Molecular basis for universal HLA-A*0201-restricted CD8+ T-cell immunity against influenza viruses.
Proc.Natl.Acad.Sci.USA, 113:4440-4445, 2016

PubMed Abstract: 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 TCRαβs 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(+)TCRαβ 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.

PubMed: 27036003
DOI: 10.1073/pnas.1603106113

Experimental method

X-RAY DIFFRACTION (1.9 Å)