HLA-B*37:01 binding "FEDLRLLSF" at 1.55Å resolution
Data provenance
Information sections
- Publication
- Peptide details
- Peptide neighbours
- Binding cleft pockets
- Chain sequences
- Downloadable data
- Data license
- Footnotes
Complex type
HLA-B*37:01
FEDLRLLSF
Species
Locus / Allele group
Broad CD8+ T cell cross-recognition of distinct influenza A strains in humans.
Newly-emerged and vaccine-mismatched influenza A viruses (IAVs) result in a rapid global spread of the virus due to minimal antibody-mediated immunity. In that case, established CD8+ T-cells can reduce disease severity. However, as mutations occur sporadically within immunogenic IAV-derived T-cell peptides, understanding of T-cell receptor (TCRαβ) cross-reactivity towards IAV variants is needed for a vaccine design. Here, we investigate TCRαβ cross-strain recognition across IAV variants within two immunodominant human IAV-specific CD8+ T-cell epitopes, HLA-B*37:01-restricted NP338-346 (B37-NP338) and HLA-A*01:01-restricted NP44-52 (A1-NP44). We find high abundance of cross-reactive TCRαβ clonotypes recognizing distinct IAV variants. Structures of the wild-type and variant peptides revealed preserved conformation of the bound peptides. Structures of a cross-reactive TCR-HLA-B37-NP338 complex suggest that the conserved conformation of the variants underpins TCR cross-reactivity. Overall, cross-reactive CD8+ T-cell responses, underpinned by conserved epitope structure, facilitates recognition of distinct IAV variants, thus CD8+ T-cell-targeted vaccines could provide protection across different IAV strains.
Structure deposition and release
Data provenance
Publication data retrieved from PDBe REST API8 and PMCe REST API9
Other structures from this publication
Data provenance
MHC:peptide complexes are visualised using PyMol. The peptide is superimposed on a consistent cutaway slice of the MHC binding cleft (displayed as a grey mesh) which best indicates the binding pockets for the P1/P5/PC positions (side view - pockets A, E, F) and for the P2/P3/PC-2 positions (top view - pockets B, C, D). In some cases peptides will use a different pocket for a specific peptide position (atypical anchoring). On some structures the peptide may appear to sterically clash with a pocket. This is an artefact of picking a standardised slice of the cleft and overlaying the peptide.
Peptide neighbours
P1
PHE
THR163
TRP167
TYR171
PHE33
TYR7
MET5
TYR159
ARG62
TYR59
GLU63
ILE66
|
P2
GLU
TYR159
ILE66
TYR7
ASN70
HIS9
GLU63
SER24
SER67
|
P3
ASP
ARG97
THR163
ASN70
TYR159
GLU63
ILE66
|
P4
LEU
ASN70
GLN65
ILE66
THR69
|
P5
ARG
ASP77
PHE116
THR73
ASN70
TYR74
TRP147
ARG97
|
P6
LEU
VAL152
ASP156
GLN155
|
P7
LEU
ALA150
THR73
VAL152
TRP147
LYS146
|
P8
SER
THR73
TRP147
LYS146
ASP77
GLU76
|
P9
PHE
LEU81
ILE95
TRP147
ILE124
ILE142
LYS146
THR80
TYR84
TYR123
ASP77
THR143
PHE116
|
Colour key
Data provenance
Neighbours are calculated by finding residues with atoms within 5Å of each other using BioPython Neighboursearch module. The list of neighbours is then sorted and filtered to inlcude only neighbours where between the peptide and the MHC Class I alpha chain.
Colours selected to match the YRB scheme. [https://www.frontiersin.org/articles/10.3389/fmolb.2015.00056/full]
A Pocket
TYR159
THR163
TRP167
TYR171
MET5
TYR59
GLU63
ILE66
TYR7
|
B Pocket
SER24
VAL34
THR45
GLU63
ILE66
SER67
TYR7
ASN70
HIS9
SER99
|
C Pocket
ASN70
THR73
TYR74
HIS9
ARG97
|
D Pocket
ASN114
GLN155
ASP156
TYR159
LEU160
SER99
|
E Pocket
ASN114
TRP147
VAL152
ASP156
ARG97
|
F Pocket
PHE116
TYR123
THR143
LYS146
TRP147
ASP77
THR80
LEU81
TYR84
ILE95
|
Colour key
Data provenance
1. Beta 2 microglobulin
Beta 2 microglobulin
|
10 20 30 40 50 60
MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKD 70 80 90 WSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM |
2. Class I alpha
HLA-B*37:01
IPD-IMGT/HLA
[ipd-imgt:HLA34729] |
10 20 30 40 50 60
GSHSMRYFHTSVSRPGRGEPRFISVGYVDDTQFVRFDSDAASPRTEPRAPWIEQEGPEYW 70 80 90 100 110 120 DRETQISKTNTQTYREDLRTLLRYYNQSEAGSHTIQRMSGCDVGPDGRLLRGYNQFAYDG 130 140 150 160 170 180 KDYIALNEDLSSWTAADTAAQITQRKWEAARVAEQDRAYLEGTCVEWLRRYLENGKETLQ 190 200 210 220 230 240 RADPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRT 250 260 270 FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEP |
3. Peptide
|
FEDLRLLSF
|
Data provenance
Sequences are retrieved via the Uniprot method of the RSCB REST API. Sequences are then compared to those derived from the PDB file and matched against sequences retrieved from the IPD-IMGT/HLA database for human sequences, or the IPD-MHC database for other species. Mouse sequences are matched against FASTA files from Uniprot. Sequences for the mature extracellular protein (signal petide and cytoplasmic tail removed) are compared to identical length sequences from the datasources mentioned before using either exact matching or Levenshtein distance based matching.
Downloadable data
Components
Data license
Footnotes
- Protein Data Bank Europe - Coordinate Server
- 1HHK - HLA-A*02:01 binding LLFGYPVYV at 2.5Å resolution - PDB entry for 1HHK
- Protein structure alignment by incremental combinatorial extension (CE) of the optimal path. - PyMol CEALIGN Method - Publication
- PyMol - PyMol.org/pymol
- Levenshtein distance - Wikipedia entry
- Protein Data Bank Europe REST API - Molecules endpoint
- 3Dmol.js: molecular visualization with WebGL - 3DMol.js - Publication
- Protein Data Bank Europe REST API - Publication endpoint
- PubMed Central Europe REST API - Articles endpoint
This work is licensed under a Creative Commons Attribution 4.0 International License.