3GIV

Antigen processing influences HIV-specific cytotoxic T lymphocyte immunodominance


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.196 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Antigen processing influences HIV-specific cytotoxic T lymphocyte immunodominance

Tenzer, S.Wee, E.Burgevin, A.Stewart-Jones, G.Friis, L.Lamberth, K.Chang, C.-H.Harndahl, M.Weimershaus, M.Gerstoft, J.Akkad, N.Klenerman, P.Fugger, L.Jones, E.Y.McMichael, A.J.Buus, S.Schild, H.van Endert, P.Iversen, A.K.N.

(2009) Nat Immunol 10: 636-646

  • DOI: https://doi.org/10.1038/ni.1728
  • Primary Citation of Related Structures:  
    3GIV

  • PubMed Abstract: 

    Although cytotoxic T lymphocytes (CTLs) in people infected with human immunodeficiency virus type 1 can potentially target multiple virus epitopes, the same few are recognized repeatedly. We show here that CTL immunodominance in regions of the human immunodeficiency virus type 1 group-associated antigen proteins p17 and p24 correlated with epitope abundance, which was strongly influenced by proteasomal digestion profiles, affinity for the transporter protein TAP, and trimming mediated by the endoplasmatic reticulum aminopeptidase ERAAP, and was moderately influenced by HLA affinity. Structural and functional analyses demonstrated that proteasomal cleavage 'preferences' modulated the number and length of epitope-containing peptides, thereby affecting the response avidity and clonality of T cells. Cleavage patterns were affected by both flanking and intraepitope CTL-escape mutations. Our analyses show that antigen processing shapes CTL response hierarchies and that viral evolution modifies cleavage patterns and suggest strategies for in vitro vaccine optimization.


  • Organizational Affiliation

    Institute of Immunology, University of Mainz, Mainz, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HLA class I histocompatibility antigen, A-2 alpha chain
A, D
275Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P04439 (Homo sapiens)
Explore P04439 
Go to UniProtKB:  P04439
PHAROS:  P04439
GTEx:  ENSG00000206503 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04439
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin
B, E
100Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P61769 (Homo sapiens)
Explore P61769 
Go to UniProtKB:  P61769
PHAROS:  P61769
GTEx:  ENSG00000166710 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP61769
Sequence Annotations
Expand
  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
HIV-1 peptide
C, F
10N/AMutation(s): 0 
UniProt
Find proteins for Q9YYH6 (Human immunodeficiency virus 1)
Explore Q9YYH6 
Go to UniProtKB:  Q9YYH6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9YYH6
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.196 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 79.581α = 90
b = 88.185β = 90.04
c = 63.864γ = 90
Software Package:
Software NamePurpose
PHASERphasing
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-06-30
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Refinement description