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6MT4

HLA-B*37:01 binding "FEDLRVSSF" at 1.55Å resolution

Data provenance

Structure downloaded from PDB Europe using the Coordinate Server. Aligned to residues 1-180 of 1HHK2 using the CEALIGN3 function of PyMol4. Chain assigment using a Levenshtein distance5 method using data from the PDBe REST API6. Organism data from PDBe REST API. Data for both of these operations from the Molecules endpoint. Structure visualised with 3DMol7.

Information sections


Complex type

Class i with peptide

1. Beta 2 microglobulin
['B']
2. Class I alpha
HLA-B*37:01
['A']
3. Peptide
FEDLRVSSF
['C']

Species


Locus / Allele group


Publication

Broad CD8+ T cell cross-recognition of distinct influenza A strains in humans.

Grant EJ, Josephs TM, Loh L, Clemens EB, Sant S, Bharadwaj M, Chen W, Rossjohn J, Gras S, Kedzierska K
Nat Commun (2018) 9, 5427 [doi:10.1038/s41467-018-07815-5]  [pubmed:30575715

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

Deposited: 2018-10-19
Released: 2019-02-13
Revised: 2019-02-13

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication


Peptide details

Length: Nonamer (9 amino acids)

Sequence: FEDLRVSSF

Interactive view
Cutaway side view (static)
Surface top view (static - coloured by atom property)
Cutaway top view (static)

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

ARG62
TYR159
TRP167
TYR171
TYR7
THR163
GLU63
MET5
PHE33
TYR59
ILE66
P2 GLU

GLU63
ASN70
HIS9
ILE66
SER24
TYR159
SER67
TYR7
P3 ASP

ILE66
THR163
GLU63
ASN70
TYR159
ARG97
P4 LEU

ILE66
THR69
GLN65
ASN70
P5 ARG

ASN70
ASP77
PHE116
ARG97
THR73
TYR74
TRP147
P6 VAL

GLN155
ASP156
VAL152
P7 SER

LYS146
THR73
TRP147
VAL152
P8 SER

THR73
GLU76
THR143
ASP77
TRP147
LYS146
P9 PHE

TYR84
TRP147
LEU81
LYS146
PHE116
ILE95
THR143
THR80
ILE142
ASP77
TYR123
ILE124

Colour key

Aromatic Hydrophobic Acidic Basic Neutral/polar

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]


Binding cleft pockets


Peptide sidechain binding pockets (static)
Peptide terminii and backbone binding residues (static)
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

Binds N-terminus Binds P1 backbone Binds P2 backbone Binds PC-1 backbone Binds C-terminus

Data provenance

N-/C-terminus and peptide backbone binding residues are assigned according to previously published information and pockets are assigned according to an adaptation of a previously published set of residues. All numbering is currently that of the 'canonical' structures of human and mouse MHC Class I molecules.

Chain sequences

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
FEDLRVSSF


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

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Please take note of the data license. Using data from this site assumes that you have read and will comply with the license.

Complete structures

Aligned structures [cif]
  1. 6MT4 assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 6MT4 assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 6MT4 assembly 1  
Peptide only [cif]
  1. 6MT4 assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/6mt4

Data license

The data above is made available under a Creative Commons CC-BY 4.0 license. This means you can copy, remix, transform, build upon and redistribute the material, but you must give appropriate credit, provide a link to the license, and indicate if changes were made.
If you use any data downloaded from this site in a publication, please cite 'https://www.histo.fyi/'. A preprint is in preparation.

Footnotes