Alpha This is a work in progress and may change. Your feedback is very welcome.
  


8GVB

HLA-A*24:02 presenting "RYPLTFGW" to Alpha/Beta T cell receptor at 3.20Å 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 and alpha beta tcr

1. Beta 2 microglobulin
['L']
2. Class I alpha
HLA-A*24:02
['H']
3. Peptide
RYPLTFGW
['P']
4. T cell receptor alpha
TRAV8
['A']
5. T cell receptor beta
TRBV7
['B']

Species


Locus / Allele group


Publication

Molecular Basis for the Recognition of HIV Nef138-8 Epitope by a Pair of Human Public T Cell Receptors.

Ma K, Chai Y, Guan J, Tan S, Qi J, Kawana-Tachikawa A, Dong T, Iwamoto A, Shi Y, Gao GF
J Immunol (2022) [doi:10.4049/jimmunol.2200191]  [pubmed:36130828

Cross-recognized public TCRs against HIV epitopes have been proposed to be important for the control of AIDS disease progression and HIV variants. The overlapping Nef138-8 and Nef138-10 peptides from the HIV Nef protein are HLA-A24-restricted immunodominant T cell epitopes, and an HIV mutant strain with a Y139F substitution in Nef protein can result in immune escape and is widespread in Japan. Here, we identified a pair of public TCRs specific to the HLA-A24-restricted Nef-138-8 epitope using PBMCs from White and Japanese patients, respectively, namely TD08 and H25-11. The gene use of the variable domain for TD08 and H25-11 is TRAV8-3, TRAJ10 for the α-chain and TRBV7-9, TRBD1*01, TRBJ2-5 for the β-chain. Both TCRs can recognize wild-type and Y2F-mutated Nef138-8 epitopes. We further determined three complex structures, including TD08/HLA-A24-Nef138-8, H25-11/HLA-A24-Nef138-8, and TD08/HLA-A24-Nef138-8 (2F). Then, we revealed the molecular basis of the public TCR binding to the peptide HLA, which mostly relies on the interaction between the TCR and HLA and can tolerate the mutation in the Nef138-8 peptide. These findings promote the molecular understanding of T cell immunity against HIV epitopes and provide an important basis for the engineering of TCRs to develop T cell-based immunotherapy against HIV infection.

Structure deposition and release

Deposited: 2022-09-14
Released: 2022-10-19
Revised: 2022-10-26

Data provenance

Publication data retrieved from PDBe REST API8 and PMCe REST API9

Other structures from this publication


Peptide details

Length: Octamer (8 amino acids)

Sequence: RYPLTFGW

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 ARG

GLY167
THR163
GLU63
TYR171
GLU62
TYR159
TYR59
TYR7
LYS66
MET5
P2 TYR

TYR159
TYR7
HIS70
LYS66
SER9
VAL67
MET45
ALA24
GLU63
MET97
PHE22
P3 PRO

TYR159
LYS66
TYR7
PHE99
P4 LEU

GLN155
GLN156
PHE99
P5 THR

THR73
MET97
LYS66
HIS70
PHE99
ALA69
TYR116
P6 PHE

GLN156
TYR116
TRP147
ASN77
GLN155
THR73
VAL152
P7 GLY

THR143
LYS146
TRP147
ASN77
THR73
P8 TRP

THR143
TYR84
ILE80
TYR123
LYS146
TRP147
ASN77
TYR116
ALA81
LEU95
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

ALA159
GLY163
ASP167
ARG171
SER5
GLU59
GLU63
GLY66
ARG7
B Pocket

ILE24
PHE34
ARG45
GLU63
GLY66
LYS67
ARG7
ALA70
PHE9
MET99
C Pocket

ALA70
GLN73
THR74
PHE9
GLN97
D Pocket

TYR114
GLU155
GLN156
ALA159
TYR160
MET99
E Pocket

TYR114
LYS147
HIS152
GLN156
GLN97
F Pocket

GLN116
ASP123
ILE143
ARG146
LYS147
GLU77
ARG80
ILE81
ARG84
THR95

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-A*24:02
IPD-IMGT/HLA
[ipd-imgt:HLA34790]
        10        20        30        40        50        60
MGSHSMRYFSTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEY
        70        80        90       100       110       120
WDEETGKVKAHSQTDRENLRIALRYYNQSEAGSHTLQMMFGCDVGSDGRFLRGYHQYAYD
       130       140       150       160       170       180
GKDYIALKEDLRSWTAADMAAQITKRKWEAAHVAEQQRAYLEGTCVDGLRRYLENGKETL
       190       200       210       220       230       240
QRTDPPKTHMTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDG
       250       260       270
TFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRW

3. Peptide
RYPLTFGW

4. T cell receptor alpha
T cell receptor alpha
TRAV8
        10        20        30        40        50        60
MAQSVTQPDIHITVSEGASLELRCNYSYGATPYLFWYVQSPGQGLQLLLKYFSGDTLVQG
        70        80        90       100       110       120
IKGFEAEFKRSQSSFNLRKPSVHWSDAAEYFCAVGFTGGGNKLTFGTGTQLKVELNIQNP
       130       140       150       160       170       180
DPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAW
       190       200
SNKSDFACANAFNNSIIPEDTFFPSPESS

5. T cell receptor beta
T cell receptor beta
TRBV7
        10        20        30        40        50        60
MDTGVSQDPRHKITKRGQNVTFRCDPISEHNRLYWYRQTLGQGPEFLTYFQNEAQLEKSR
        70        80        90       100       110       120
LLSDRFSAERPKGSFSTLEIQRTEQGDSAMYLCASSDRDRVPETQYFGPGTRLLVLEDLK
       130       140       150       160       170       180
NVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLK
       190       200       210       220       230       240
EQPALNDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAE

AWGRAD


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

Data can be downloaded to your local machine from the links below.
Clicking on the clipboard icon will copy the url for the data to your clipboard.
This can then be used to load the structure/data directly from the url into an application like PyMol (for 3D structures) using the load command:
   e.g. load http://www.histo.fyi/structures/downloads/1hhk_1_peptide.cif
or in the case of JSON formatted files to retrieve it and use it as part of notebooks such as Jupyter or GoogleColab.
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. 8GVB assembly 1  

Components

MHC Class I alpha chain [cif]
  1. 8GVB assembly 1  
MHC Class I antigen binding domain (alpha1/alpha2) [cif]
  1. 8GVB assembly 1  
Peptide only [cif]
  1. 8GVB assembly 1  

Derived data

Data for this page [json]
https://api.histo.fyi/v1/structures/8gvb

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