1KLU

Crystal structure of HLA-DR1/TPI(23-37) complexed with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.93 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.208 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Minor structural changes in a mutated human melanoma antigen correspond to dramatically enhanced stimulation of a CD4+ tumor-infiltrating lymphocyte line.

Sundberg, E.J.Sawicki, M.W.Southwood, S.Andersen, P.S.Sette, A.Mariuzza, R.A.

(2002) J Mol Biol 319: 449-461

  • DOI: https://doi.org/10.1016/S0022-2836(02)00370-4
  • Primary Citation of Related Structures:  
    1KLG, 1KLU

  • PubMed Abstract: 

    While most immunotherapies for cancer have focused on eliciting specific CD8+ cytotoxic T lymphocyte killing of tumor cells, a mounting body of evidence suggests that stimulation of anti-tumor CD4+ T cell help may be required for highly effective therapy. Several MHC class II-restricted tumor antigens that specifically activate such CD4+ helper T lymphocytes have now been identified, including one from a melanoma tumor that is caused by a single base-pair mutation in the glycolytic enzyme triosephosphate isomerase. This mutation results in the conversion of a threonine residue to isoleucine within the antigenic epitope, concomitant with a greater than five log-fold increase in stimulation of a CD4+ tumor-infiltrating lymphocyte line. Here, we present the crystal structures of HLA-DR1 in complex with both wild-type and mutant TPI peptide antigens, the first structures of tumor peptide antigen/MHC class II complexes recognized by CD4+ T cells to be reported. These structures show that very minor changes in the binding surface for T cell receptor correspond to the dramatic differences in T cell stimulation. Defining the structural basis by which CD4+ T cell help is invoked in an anti-tumor immune response will likely aid the design of more effective cancer immunotherapies.


  • Organizational Affiliation

    Center for Advanced Research in Biotechnology, W. M. Keck Laboratory for Structural Biology, University of Maryland Biotechnology Institute, 9600 Gudelsky Drive, Rockville, MD 20850, USA. sundberg@umbi.umd.edu


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HLA CLASS II HISTOCOMPATIBILITY ANTIGEN, DR ALPHA CHAIN179Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P01903 (Homo sapiens)
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Go to UniProtKB:  P01903
PHAROS:  P01903
GTEx:  ENSG00000204287 
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UniProt GroupP01903
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
HLA CLASS II HISTOCOMPATIBILITY ANTIGEN, DR-1 BETA CHAIN190Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P01911 (Homo sapiens)
Explore P01911 
Go to UniProtKB:  P01911
PHAROS:  P01911
GTEx:  ENSG00000196126 
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UniProt GroupP01911
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Triosephosphate isomerase peptide15N/AMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P60174 (Homo sapiens)
Explore P60174 
Go to UniProtKB:  P60174
PHAROS:  P60174
GTEx:  ENSG00000111669 
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UniProt GroupP60174
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
ENTEROTOXIN TYPE C-3239Staphylococcus aureusMutation(s): 4 
UniProt
Find proteins for P0A0L5 (Staphylococcus aureus)
Explore P0A0L5 
Go to UniProtKB:  P0A0L5
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UniProt GroupP0A0L5
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.93 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.208 
  • Space Group: H 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 171.296α = 90
b = 171.296β = 90
c = 121.024γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
CNSrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-08-02
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2021-10-27
    Changes: Database references