PMID- 21231985
OWN - NLM
STAT- MEDLINE
DCOM- 20110609
LR  - 20111117
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Linking)
VI  - 102
IP  - 4
DP  - 2011 Apr
TI  - Analysis of HLA-A24-restricted peptides of carcinoembryonic antigen using a novel 
      structure-based peptide-HLA docking algorithm.
PG  - 690-6
LID - 10.1111/j.1349-7006.2011.01866.x [doi]
AB  - Carcinoembryonic antigen (CEA) is a very common tumor marker because many types 
      of solid cancer usually produce a variety of CEA and a highly sensitive measuring 
      kit has been developed. However, immunological responses associated with CEA have 
      not been fully characterized, and specifically a weak immunogenicity of CEA 
      protein as a tumor antigen is reported in human leukocyte antigen 
      (HLA)-A24-restricted CEA peptide-based cancer immunotherapy. These observations 
      demonstrated that immunogenic and potent HLA-A24-restricted CTL epitope peptides 
      derived from CEA protein are seemingly difficult to predict using a conventional 
      bioinformatics approach based on primary amino acid sequence. In the present 
      study, we developed an in silico docking simulation assay system of binding 
      affinity between HLA-A24 protein and A24-restricted peptides using two software 
      packages, AutoDock and MODELLER, and a crystal structure of HLA-A24 protein 
      obtained from the Protein Data Bank. We compared the current assay system with 
      HLA-peptide binding predictions of the bioinformatics and molecular analysis 
      section (BIMAS) in terms of the prediction capability using MHC stabilization and 
      peptide-stimulated CTL induction assays for CEA and other HLA-A24 peptides. The 
      MHC stabilization score was inversely correlated with the affinity calculated in 
      the docking simulation alone (r = -0.589, P = 0.015), not with BIMAS score or the 
      IFN-gamma production index. On the other hand, BIMAS was not significantly correlated 
      with any other parameters. These results suggested that our in silico assay 
      system has potential advantages in efficiency of epitope prediction over BIMAS 
      and ease of use for bioinformaticians.
CI  - (c) 2011 Japanese Cancer Association.
FAU - Nakamura, Yoji
AU  - Nakamura Y
AD  - Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shimonagakubo, 
      Nagaizumi-cho, Sunto-gun, Shizuoka, Japan.
FAU - Tai, Sachiko
AU  - Tai S
FAU - Oshita, Chie
AU  - Oshita C
FAU - Iizuka, Akira
AU  - Iizuka A
FAU - Ashizawa, Tadashi
AU  - Ashizawa T
FAU - Saito, Shuji
AU  - Saito S
FAU - Yamaguchi, Shigeki
AU  - Yamaguchi S
FAU - Kondo, Haruhiko
AU  - Kondo H
FAU - Yamaguchi, Ken
AU  - Yamaguchi K
FAU - Akiyama, Yasuto
AU  - Akiyama Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110220
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Carcinoembryonic Antigen)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A24 Antigen)
RN  - 0 (Peptide Fragments)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Antigens, Neoplasm/immunology/metabolism
MH  - Carcinoembryonic Antigen/chemistry/*metabolism
MH  - Computer Simulation
MH  - Databases, Factual
MH  - HLA-A Antigens/chemistry/*metabolism
MH  - HLA-A24 Antigen
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Neoplasms/immunology/metabolism
MH  - Peptide Fragments
MH  - Protein Conformation
MH  - T-Lymphocytes, Cytotoxic/immunology
EDAT- 2011/01/15 06:00
MHDA- 2011/06/10 06:00
CRDT- 2011/01/15 06:00
PHST- 2011/01/15 06:00 [entrez]
PHST- 2011/01/15 06:00 [pubmed]
PHST- 2011/06/10 06:00 [medline]
AID - 10.1111/j.1349-7006.2011.01866.x [doi]
PST - ppublish
SO  - Cancer Sci. 2011 Apr;102(4):690-6. doi: 10.1111/j.1349-7006.2011.01866.x. Epub 
      2011 Feb 20.