5MEN

Human Leukocyte Antigen A02 presenting ILAKFLHWL, in complex with cognate T-Cell Receptor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.81 Å
  • R-Value Free: 0.272 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.193 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structural Mechanism Underpinning Cross-reactivity of a CD8+ T-cell Clone That Recognizes a Peptide Derived from Human Telomerase Reverse Transcriptase.

Cole, D.K.van den Berg, H.A.Lloyd, A.Crowther, M.D.Beck, K.Ekeruche-Makinde, J.Miles, J.J.Bulek, A.M.Dolton, G.Schauenburg, A.J.Wall, A.Fuller, A.Clement, M.Laugel, B.Rizkallah, P.J.Wooldridge, L.Sewell, A.K.

(2017) J Biol Chem 292: 802-813

  • DOI: https://doi.org/10.1074/jbc.M116.741603
  • Primary Citation of Related Structures:  
    5MEN, 5MEO, 5MEP, 5MEQ, 5MER

  • PubMed Abstract: 

    T-cell cross-reactivity is essential for effective immune surveillance but has also been implicated as a pathway to autoimmunity. Previous studies have demonstrated that T-cell receptors (TCRs) that focus on a minimal motif within the peptide are able to facilitate a high level of T-cell cross-reactivity. However, the structural database shows that most TCRs exhibit less focused antigen binding involving contact with more peptide residues. To further explore the structural features that allow the clonally expressed TCR to functionally engage with multiple peptide-major histocompatibility complexes (pMHCs), we examined the ILA1 CD8 + T-cell clone that responds to a peptide sequence derived from human telomerase reverse transcriptase. The ILA1 TCR contacted its pMHC with a broad peptide binding footprint encompassing spatially distant peptide residues. Despite the lack of focused TCR-peptide binding, the ILA1 T-cell clone was still cross-reactive. Overall, the TCR-peptide contacts apparent in the structure correlated well with the level of degeneracy at different peptide positions. Thus, the ILA1 TCR was less tolerant of changes at peptide residues that were at, or adjacent to, key contact sites. This study provides new insights into the molecular mechanisms that control T-cell cross-reactivity with important implications for pathogen surveillance, autoimmunity, and transplant rejection.


  • Organizational Affiliation

    From the Division of Infection and Immunity and Systems Immunity Research Institute, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, United Kingdom, coledk@cf.ac.uk.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HLA class I histocompatibility antigen, A-2 alpha chain276Homo sapiensMutation(s): 0 
Gene Names: HLA-AHLAA
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Find proteins for P04439 (Homo sapiens)
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PHAROS:  P04439
GTEx:  ENSG00000206503 
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UniProt GroupP04439
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin100Homo sapiensMutation(s): 0 
Gene Names: B2MCDABP0092HDCMA22P
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Find proteins for P61769 (Homo sapiens)
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PHAROS:  P61769
GTEx:  ENSG00000166710 
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UniProt GroupP61769
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
ILE-LEU-ALA-LYS-PHE-LEU-HIS-TRP-LEU9Homo sapiensMutation(s): 0 
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Find proteins for O14746 (Homo sapiens)
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PHAROS:  O14746
GTEx:  ENSG00000164362 
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UniProt GroupO14746
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Protein TRAV22,Human nkt tcr alpha chain200Homo sapiensMutation(s): 0 
Gene Names: TRAV22B2MHDCMA22P
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Find proteins for A0A0B4J277 (Homo sapiens)
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Go to UniProtKB:  A0A0B4J277
PHAROS:  A0A0B4J277
GTEx:  ENSG00000211802 
Find proteins for K7N5M3 (Homo sapiens)
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UniProt GroupsK7N5M3A0A0B4J277
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Entity ID: 5
MoleculeChains Sequence LengthOrganismDetailsImage
Protein TRBV6-5,Human nkt tcr beta chain240Homo sapiensMutation(s): 0 
Gene Names: TRBV6-5B2MHDCMA22P
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PHAROS:  A0A0K0K1A5
GTEx:  ENSG00000211721 
Find proteins for K7N5M4 (Homo sapiens)
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UniProt GroupsK7N5M4A0A0K0K1A5
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Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SO4
Query on SO4

Download Ideal Coordinates CCD File 
I [auth A],
J [auth A],
K [auth A],
O [auth B],
P [auth E]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

Download Ideal Coordinates CCD File 
H [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A],
L [auth B],
M [auth B],
N [auth B]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.81 Å
  • R-Value Free: 0.272 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.193 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 93.16α = 90
b = 48.69β = 108.15
c = 118.1γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction
XDSdata reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-12-07
    Type: Initial release
  • Version 1.1: 2016-12-14
    Changes: Database references
  • Version 1.2: 2017-02-01
    Changes: Database references
  • Version 1.3: 2017-03-22
    Changes: Refinement description
  • Version 1.4: 2024-01-17
    Changes: Data collection, Database references, Refinement description