3FFC

HLA-B*08:01 presenting "FLRGRAYGL" to Alpha/Beta T cell receptor at 2.80Å 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']

2. Class I alpha
HLA-B*08:01

['A', 'F']

3. Peptide
FLRGRAYGL

['C', 'H']

4. T cell receptor alpha
TRAV14

['D']

5. T cell receptor beta
TRBV11

['E']

Information on this structure on STCRdab.

Species

Homo sapiens (Human)

Locus / Allele group

HLA-B / HLA-B*08

Publication

The shaping of T cell receptor recognition by self-tolerance.

Gras S, Burrows SR, Kjer-Nielsen L, Clements CS, Liu YC, Sullivan LC, Bell MJ, Brooks AG, Purcell AW, McCluskey J, Rossjohn J

Immunity (2009) 30, 193-203 [doi:10.1016/j.immuni.2008.11.011] [pubmed:19167249]

During selection of the T cell repertoire, the immune system navigates the subtle distinction between self-restriction and self-tolerance, yet how this is achieved is unclear. Here we describe how self-tolerance toward a trans-HLA (human leukocyte antigen) allotype shapes T cell receptor (TCR) recognition of an Epstein-Barr virus (EBV) determinant (FLRGRAYGL). The recognition of HLA-B8-FLRGRAYGL by two archetypal TCRs was compared. One was a publicly selected TCR, LC13, that is alloreactive with HLA-B44; the other, CF34, lacks HLA-B44 reactivity because it arises when HLA-B44 is coinherited in trans with HLA-B8. Whereas the alloreactive LC13 TCR docked at the C terminus of HLA-B8-FLRGRAYGL, the CF34 TCR docked at the N terminus of HLA-B8-FLRGRAYGL, which coincided with a polymorphic region between HLA-B8 and HLA-B44. The markedly contrasting footprints of the LC13 and CF34 TCRs provided a portrait of how self-tolerance shapes the specificity of TCRs selected into the immune repertoire.

Structure deposition and release

Deposited: 2008-12-03

Released: 2009-01-27

Revised: 2019-11-13

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: FLRGRAYGL

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

ASN63

ILE66

MET5

TYR159

TYR59

TRP167

PHE33

ARG62

TYR7

TYR171

THR163

P2 LEU

ASP9

TYR7

TYR99

SER24

ASN70

ASN63

ILE66

PHE36

PHE67

TYR159

P3 ARG

ILE66

TYR159

ASP156

ASN70

SER97

TYR116

ASN114

TYR99

P4 GLY

ASN70

ILE66

ASP156

P5 ARG

ASN70

ASP9

ASP74

TYR116

TYR99

SER97

THR69

THR73

P6 ALA

GLN155

THR73

P7 TYR

TRP147

VAL152

ALA150

GLN155

THR73

GLU76

LYS146

P8 GLY

THR73

GLU76

LYS146

SER77

TRP147

P9 LEU

ILE124

TYR116

TYR84

LEU81

TYR123

GLU76

LYS146

SER77

LEU95

TRP147

THR143

ASN80

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

ASN63

ILE66

TYR7

B Pocket

SER24

VAL34

GLU45

ASN63

ILE66

PHE67

TYR7

ASN70

ASP9

TYR99

C Pocket

ASN70

THR73

ASP74

ASP9

SER97

D Pocket

ASN114

GLN155

ASP156

TYR159

LEU160

TYR99

E Pocket

ASN114

TRP147

VAL152

ASP156

SER97

F Pocket

TYR116

TYR123

THR143

LYS146

TRP147

SER77

ASN80

LEU81

TYR84

LEU95

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-B08:01 IPD-IMGT/HLA* [ipd-imgt:HLA34671]	10 20 30 40 50 60 GSHSMRYFDTAMSRPGRGEPRFISVGYVDDTQFVRFDSDAASPREEPRAPWIEQEGPEYW 70 80 90 100 110 120 DRNTQIFKTNTQTDRESLRNLRGYYNQSEAGSHTLQSMYGCDVGPDGRLLRGHNQYAYDG 130 140 150 160 170 180 KDYIALNEDLRSWTAADTAAQITQRKWEAARVAEQDRAYLEGTCVEWLRRYLENGKDTLE 190 200 210 220 230 240 RADPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRT 250 260 270 FQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEPS

3. Peptide	FLRGRAYGL

4. T cell receptor alpha T cell receptor alpha TRAV14	10 20 30 40 50 60 KITQTQPGMFVQEKEAVTLDCTYDTSDPSYGLFWYKQPSSGEMIFVIYQGSYDQGNATEG 70 80 90 100 110 120 RYSLNFQKARKSANLVISASQLGDSAMYFCAMREDTGNQFYFGTGTSLTVIPNIQNPDPA 130 140 150 160 170 180 VYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNK 190 200 SDFACANAFNNSIIPEDTFFPS

5. T cell receptor beta T cell receptor beta TRBV11	10 20 30 40 50 60 MGVAQSPRYKIIEKRQSVAFWCNPISGHATLYWYQQILGQGPKLLIQFQNNGVVDDSQLP 70 80 90 100 110 120 KDRFSAERLKGVDSTLKIQPAKLEDSAVYLCASSFTWTSGGATDTQYFGPGTRLTVLEDL 130 140 150 160 170 180 KNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPL 190 200 210 220 230 240 KEQPALNDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSA EAWGRAD

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]

3FFC assembly 1

Components

MHC Class I alpha chain [cif]

3FFC assembly 1

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

3FFC assembly 1

Peptide only [cif]

3FFC assembly 1

Derived data

Data for this page [json]

https://api.histo.fyi/v1/structures/3ffc

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.

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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.