6RPB

HLA-A*02:01 presenting "SLLMWITQV" to Alpha/Beta T cell receptor at 2.50Å 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', 'G', 'L', 'Q']

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

['A', 'F', 'K', 'P']

3. Peptide
SLLMWITQV

['C', 'H', 'M', 'R']

4. T cell receptor alpha
TRAV12

['D']

5. T cell receptor beta
TRBV6

['E']

Information on this structure on STCRdab.

Species

Homo sapiens (Human)

Locus / Allele group

HLA-A / HLA-A*02

Publication

TCRs with Distinct Specificity Profiles Use Different Binding Modes to Engage an Identical Peptide-HLA Complex.

Coles CH, Mulvaney RM, Malla S, Walker A, Smith KJ, Lloyd A, Lowe KL, McCully ML, Martinez Hague R, Aleksic M, Harper J, Paston SJ, Donnellan Z, Chester F, Wiederhold K, Robinson RA, Knox A, Stacey AR, Dukes J, Baston E, Griffin S, Jakobsen BK, Vuidepot A, Harper S

J. Immunol. (2020) [doi:10.4049/jimmunol.1900915] [pubmed:32102902]

The molecular rules driving TCR cross-reactivity are poorly understood and, consequently, it is unclear the extent to which TCRs targeting the same Ag recognize the same off-target peptides. We determined TCR-peptide-HLA crystal structures and, using a single-chain peptide-HLA phage library, we generated peptide specificity profiles for three newly identified human TCRs specific for the cancer testis Ag NY-ESO-1157-165-HLA-A2. Two TCRs engaged the same central peptide feature, although were more permissive at peripheral peptide positions and, accordingly, possessed partially overlapping peptide specificity profiles. The third TCR engaged a flipped peptide conformation, leading to the recognition of off-target peptides sharing little similarity with the cognate peptide. These data show that TCRs specific for a cognate peptide recognize discrete peptide repertoires and reconciles how an individual's limited TCR repertoire following negative selection in the thymus is able to recognize a vastly larger antigenic pool.

Structure deposition and release

Deposited: 2019-05-14

Released: 2020-01-15

Revised: 2020-04-08

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: SLLMWITQV

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 SER

TRP167

PHE33

MET5

TYR159

TYR59

TYR7

THR163

LYS66

TYR171

GLU63

P2 LEU

TYR159

PHE9

TYR7

LYS66

HIS70

TYR99

GLU63

MET45

VAL67

P3 LEU

ARG97

TYR159

LYS66

LEU156

HIS70

TYR99

HIS114

P4 MET

LYS66

P5 TRP

GLN155

P6 ILE

ALA69

THR73

ARG97

HIS70

P7 THR

TRP147

VAL152

GLN155

LYS146

ALA150

THR73

ARG97

P8 GLN

ASP77

THR143

LYS146

THR73

VAL76

TRP147

P9 VAL

TRP147

TYR84

ASP77

THR143

LYS146

TYR116

TYR123

THR80

LEU81

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

GLU167

ARG171

SER5

GLU59

GLY63

ARG66

ARG7

B Pocket

ILE24

PHE34

ARG45

GLY63

ARG66

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

THR143

HIS146

LYS147

VAL77

GLY80

THR81

GLY84

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

3. Peptide	SLLMWITQV

4. T cell receptor alpha T cell receptor alpha TRAV12	10 20 30 40 50 60 MQKEVEQNSGPLSVPEGAIASLNCTYSDRGSQSFFWYRQYSGKSPELIMFIYSDGDKEDG 70 80 90 100 110 120 RFTAQLNRASQYVSLLIRDSQPSDSATYLCAVKSGGSYIPTFGRGTSLIVHPYIQNPDPA 130 140 150 160 170 180 VYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNK 190 200 SDFACANAFNNSIIPEDTFFPSPESS

5. T cell receptor beta T cell receptor beta TRBV6	10 20 30 40 50 60 MNAGVTQTPKFQVLKTGQSMTLQCAQDMNHEYMSWYRQDPGMGLRLIHYSVGAGITDKGE 70 80 90 100 110 120 VPNGYNVSRSTTEDFPLRLLSAAPSQTSVYFCASSYLNRDSALDFGPGTRLTVLEDLKNV 130 140 150 160 170 180 FPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKEQ 190 200 210 220 230 240 PALNDSRYALSSRLRVSATFWQDPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAW GRAD

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]

6RPB assembly 1

Components

MHC Class I alpha chain [cif]

6RPB assembly 1

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

6RPB assembly 1

Peptide only [cif]

6RPB assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/6rpb

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.