SLA-1*14:02 binding "EFEDLTFLA" at 1.43Å resolution
Data provenance
Information sections
- Publication
- Peptide details
- Peptide neighbours
- Binding cleft pockets
- Chain sequences
- Downloadable data
- Data license
- Footnotes
Complex type
SLA-1*14:02
EFEDLTFLA
Species
Locus / Allele group
Induction of influenza-specific local CD8 T-cells in the respiratory tract after aerosol delivery of vaccine antigen or virus in the Babraham inbred pig.
There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume. It may also be an important vector in the birds to human infection cycle. A major drawback of the current pig model is the inability to analyze antigen-specific CD8+ T-cell responses, which are critical to respiratory immunity. Here we address this knowledge gap using an established in-bred pig model with a high degree of genetic identity between individuals, including the MHC (Swine Leukocyte Antigen (SLA)) locus. We developed a toolset that included long-term in vitro pig T-cell culture and cloning and identification of novel immunodominant influenza-derived T-cell epitopes. We also generated structures of the two SLA class I molecules found in these animals presenting the immunodominant epitopes. These structures allowed definition of the primary anchor points for epitopes in the SLA binding groove and established SLA binding motifs that were used to successfully predict other influenza-derived peptide sequences capable of stimulating T-cells. Peptide-SLA tetramers were constructed and used to track influenza-specific T-cells ex vivo in blood, the lungs and draining lymph nodes. Aerosol immunization with attenuated single cycle influenza viruses (S-FLU) induced large numbers of CD8+ T-cells specific for conserved NP peptides in the respiratory tract. Collectively, these data substantially increase the utility of pigs as an effective model for studying protective local cellular immunity against respiratory pathogens.
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
GLU
TYR8
ASN67
SER168
TYR172
TYR100
TYR160
THR164
TYR60
ASN64
LEU6
ARG63
|
P2
PHE
SER71
ALA25
TYR8
ASN67
TRP98
TYR100
MET46
SER10
TYR160
ASN64
VAL68
|
P3
GLU
TYR160
SER71
ASN67
TRP98
HIS156
TYR100
TRP157
|
P4
ASP
ASN67
HIS156
|
P5
LEU
HIS156
|
P6
THR
TRP98
ILE74
ASN75
SER71
|
P7
PHE
ALA151
HIS156
ILE74
TRP157
ASN78
ALA153
TRP148
|
P8
LEU
ILE74
VAL77
ASN78
LYS147
TRP148
|
P9
ALA
SER144
LYS147
LEU82
TRP148
ILE143
ASN78
THR81
TYR85
TYR124
|
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
SER159
GLY163
GLU167
ARG171
SER5
GLU59
ARG63
ARG66
SER7
|
B Pocket
ILE24
PHE34
ARG45
ARG63
ARG66
ASN67
SER7
GLY70
PHE9
MET99
|
C Pocket
GLY70
GLN73
ILE74
PHE9
GLN97
|
D Pocket
TYR114
GLU155
HIS156
SER159
TYR160
MET99
|
E Pocket
TYR114
LYS147
ASP152
HIS156
GLN97
|
F Pocket
GLN116
ASP123
ILE143
ARG146
LYS147
VAL77
LYS80
THR81
GLY84
THR95
|
Colour key
Data provenance
1. Beta 2 microglobulin
Beta 2 microglobulin
|
10 20 30 40 50 60
MVARPPKVQVYSRHPAENGKPNYLNCYVSGFHPPQIEIDLLKNGEKMNAEQSDLSFSKDW 70 80 90 SFYLLVHTEFTPNAVDQYSCRVKHVTLDKPKIVKWDRDH |
2. Class I alpha
SLA-1*14:02
IPD-MHC
[ipd-mhc:SLA06136] |
10 20 30 40 50 60
MGPHSLSYFSTAVSRPDRGDSRFIAVGYVDDTQFVRFDSDAPNPRMEPRAPWIQQEGQEY 70 80 90 100 110 120 WDRNTRNVMGSAQINRVNLKTLRGYYNQSEAGSHTLQWMYGCYLGPDGLLLRGYDQFAYD 130 140 150 160 170 180 GADYLALNEDLRSWTAADMAAQISKRKWEAADAAEHWRSYLQGTCVESLRRYLQMGKDTL 190 200 210 220 230 240 QRAEPPKTHVTRHPSSDLGVTLRCWALGFHPKEISLTWQREGQDQSQDMELVETRPSGDG 250 260 270 TFQKWAALVVPPGEEQSYTCHVQHEGLQEPLTLRWDP |
3. Peptide
|
EFEDLTFLA
|
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.