7N1F

HLA-A*02:01 presenting "YLQPRTFLL" to Alpha/Beta T cell receptor at 2.39Å 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.

Complex type

Class i with peptide and alpha beta tcr

1. Beta 2 microglobulin

['B']

2. Class I alpha
HLA-A*02:01

['A']

3. Peptide
YLQPRTFLL

['C']

4. T cell receptor alpha
TRAV12

['D']

5. T cell receptor beta
TRBV7

['E']

Information on this structure on STCRdab.

Species

Homo sapiens (Human)

Locus / Allele group

HLA-A / HLA-A*02

Publication

Structural assessment of HLA-A2-restricted SARS-CoV-2 spike epitopes recognized by public and private T-cell receptors.

Wu D, Kolesnikov A, Yin R, Guest JD, Gowthaman R, Shmelev A, Serdyuk Y, Dianov DV, Efimov GA, Pierce BG, Mariuzza RA

Nat Commun (2022) 13, 19 [doi:10.1038/s41467-021-27669-8] [pubmed:35013235]

T cells play a vital role in combatting SARS-CoV-2 and forming long-term memory responses. Whereas extensive structural information is available on neutralizing antibodies against SARS-CoV-2, such information on SARS-CoV-2-specific T-cell receptors (TCRs) bound to their peptide-MHC targets is lacking. Here we determine the structures of a public and a private TCR from COVID-19 convalescent patients in complex with HLA-A2 and two SARS-CoV-2 spike protein epitopes (YLQ and RLQ). The structures reveal the basis for selection of particular TRAV and TRBV germline genes by the public but not the private TCR, and for the ability of the TCRs to recognize natural variants of RLQ but not YLQ. Neither TCR recognizes homologous epitopes from human seasonal coronaviruses. By elucidating the mechanism for TCR recognition of an immunodominant yet variable epitope (YLQ) and a conserved but less commonly targeted epitope (RLQ), this study can inform prospective efforts to design vaccines to elicit pan-coronavirus immunity.

Structure deposition and release

Deposited: 2021-05-27

Released: 2021-07-28

Revised: 2022-02-02

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: YLQPRTFLL

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 TYR

TRP167

TYR7

TYR171

PHE33

THR163

TYR159

TYR59

GLU63

LYS66

MET5

P2 LEU

GLU63

VAL67

TYR99

PHE9

MET45

TYR7

HIS70

TYR159

LYS66

P3 GLN

LEU156

GLN155

HIS70

TYR159

TYR99

LYS66

HIS114

ARG97

P4 PRO

TYR159

LYS66

P5 ARG

HIS70

ARG97

GLN155

P6 THR

ALA69

ARG97

HIS70

THR73

P7 PHE

TRP147

LEU156

ARG97

TYR116

GLN155

ASP77

HIS114

THR73

VAL152

P8 LEU

LYS146

THR73

VAL76

ASP77

TRP147

P9 LEU

VAL95

THR142

LYS146

THR143

TYR123

ASP77

ILE124

THR80

TYR116

LEU81

TRP147

TYR84

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

LYS66

TYR7

B Pocket

ALA24

VAL34

MET45

GLU63

LYS66

VAL67

TYR7

HIS70

PHE9

TYR99

C Pocket

HIS70

THR73

HIS74

PHE9

ARG97

D Pocket

HIS114

GLN155

LEU156

TYR159

LEU160

TYR99

E Pocket

HIS114

TRP147

VAL152

LEU156

ARG97

F Pocket

TYR116

TYR123

THR143

LYS146

TRP147

ASP77

THR80

LEU81

TYR84

VAL95

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-A02:01 IPD-IMGT/HLA* [ipd-imgt:HLA35266]	10 20 30 40 50 60 GSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYW 70 80 90 100 110 120 DGETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDG 130 140 150 160 170 180 KDYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENGKETLQ 190 200 210 220 230 240 RTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGT 250 260 270 FQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLRWE

3. Peptide	YLQPRTFLL

4. T cell receptor alpha T cell receptor alpha TRAV12	10 20 30 40 50 60 MQKEVEQNSGPLSVPEGAIASLNCTYSDRGSQSFFWYRQYSGKSPELIMFIYSNGDKEDG 70 80 90 100 110 120 RFTAQLNKASQYVSLLIRDSQPSDSATYLCAVNRDDKIIFGKGTRLHILPNIQNPDPAVY 130 140 150 160 170 180 QLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSD 190 200 FACANAFNNSIIPEDTFFPSPESS

5. T cell receptor beta T cell receptor beta TRBV7	10 20 30 40 50 60 MDTGVSQNPRHKITKRGQNVTFRCDPISEHNRLYWYRQTLGQGPEFLTYFQNEAQLEKSR 70 80 90 100 110 120 LLSDRFSAERPKGSFSTLEIQRTEQGDSAMYLCASSPDIEQYFGPGTRLTVTEDLKNVFP 130 140 150 160 170 180 PEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKEQPA 190 200 210 220 230 240 LNDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGR AD

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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Complete structures

Aligned structures [cif]

7N1F assembly 1

Components

MHC Class I alpha chain [cif]

7N1F assembly 1

MHC Class I antigen binding domain (alpha1/alpha2) [cif]

7N1F assembly 1

Peptide only [cif]

7N1F assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/7n1f

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

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.