PMID- 19232439
OWN - NLM
STAT- MEDLINE
DCOM- 20090609
LR  - 20211020
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 46
IP  - 8-9
DP  - 2009 May
TI  - 3-Layer-based analysis of peptide-MHC interaction: in silico prediction, peptide 
      binding affinity and T cell activation in a relevant allergen-specific model.
PG  - 1839-44
LID - 10.1016/j.molimm.2009.01.009 [doi]
AB  - CD4+ T cells recognize peptides bound to major histocompatibility complex (MHC) 
      class II molecules on the surface of antigen presenting cells by their T cell 
      receptor (TCR). Using a well-characterized allergen-specific model we studied 
      peptide/MHC (pMHC) interactions by combining computational methods with 
      experimental analyses. A 12-mer and an 18-mer peptide, both containing the human 
      leukocyte antigen (HLA)-DR1-restricted, immunodominant T cell epitope of Art v 1, 
      the major mugwort pollen allergen, were compared. A Molecular Dynamics simulation 
      for a real time of 20 ns using GROMACS was performed. To this aim, the peptides 
      were modelled into the binding groove of HLA-DRB1*0101 using different amino acid 
      substitution tools. Binding of synthetic peptides to purified HLA-DRB1*0101 
      molecules was analysed in competition assays. The potency of the peptides to 
      activate Art v 1-specific T cells was assessed using oligo- and monoclonal Art v 
      1-specific T cell cultures expanded from mugwort allergic individuals. All 
      approaches revealed that the 18-mer peptide possessed higher HLA DR affinity as 
      compared to the 12-mer. Computer modelling indicated that a loop-like structure 
      within the additional N-terminal peptide flanking region of the 18-mer 
      contributed to the pMHC interaction. Our approach, to combine computational 
      methods validated by experimental results, demonstrates that Molecular Dynamics 
      simulation may be a useful tool for the prediction of pMHC interactions in the 
      future with possible applications in T cell-based immunotherapy e.g. in Type I 
      allergy.
FAU - Knapp, Bernhard
AU  - Knapp B
AD  - Department for Biomedical Computersimulation and Bioinformatics, Medical 
      University of Vienna, Austria. bernhard.knapp@meduniwien.ac.at
FAU - Omasits, Ulrich
AU  - Omasits U
FAU - Bohle, Barbara
AU  - Bohle B
FAU - Maillere, Bernard
AU  - Maillere B
FAU - Ebner, Christof
AU  - Ebner C
FAU - Schreiner, Wolfgang
AU  - Schreiner W
FAU - Jahn-Schmid, Beatrice
AU  - Jahn-Schmid B
LA  - eng
GR  - P 20011/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
DEP - 20090215
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Allergens)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Peptides)
SB  - IM
MH  - Allergens/immunology
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Antigen Presentation/immunology
MH  - Computer Simulation
MH  - Epitope Mapping/methods
MH  - Forecasting
MH  - HLA-DR Antigens/chemistry/genetics/immunology/*metabolism
MH  - HLA-DRB1 Chains
MH  - Humans
MH  - Imaging, Three-Dimensional/methods
MH  - Lymphocyte Activation/*immunology
MH  - Major Histocompatibility Complex/immunology
MH  - Models, Molecular
MH  - Peptides/chemistry/immunology/*metabolism
MH  - Protein Binding
MH  - Protein Conformation
MH  - Substrate Specificity
MH  - T-Lymphocytes/*immunology/metabolism
EDAT- 2009/02/24 09:00
MHDA- 2009/06/10 09:00
CRDT- 2009/02/24 09:00
PHST- 2008/11/07 00:00 [received]
PHST- 2009/01/08 00:00 [revised]
PHST- 2009/01/09 00:00 [accepted]
PHST- 2009/02/24 09:00 [entrez]
PHST- 2009/02/24 09:00 [pubmed]
PHST- 2009/06/10 09:00 [medline]
AID - S0161-5890(09)00037-6 [pii]
AID - 10.1016/j.molimm.2009.01.009 [doi]
PST - ppublish
SO  - Mol Immunol. 2009 May;46(8-9):1839-44. doi: 10.1016/j.molimm.2009.01.009. Epub 
      2009 Feb 15.