PMID- 21092580
OWN - NLM
STAT- MEDLINE
DCOM- 20110823
LR  - 20111117
IS  - 0529-5815 (Print)
IS  - 0529-5815 (Linking)
VI  - 48
IP  - 18
DP  - 2010 Sep 15
TI  - [Pentamer guided HLA-restricted epitope identification for mucoprotein 4 antigen 
      of pancreatic ductal adenocarcinoma].
PG  - 1416-24
AB  - OBJECTIVES: To identify HLA-restricted epitope of mucoprotein 4 (MUC4) antigen as 
      a tumor associated antigen of pancreatic ductal adenocarcinoma (PDAC), and to 
      validate its natural presentation in PDAC patient peripheral blood. METHODS: Two 
      epitope prediction databases (SYFPEITHI and ProPred-I) were used to predict 
      HLA-A*0201 restricted MUC4 epitope, T2 cell assay was used to determine the 
      peptide binding affinity with HLA-A*0201 molecule. Dendritic cells (DCs) were 
      induced from the HLA-A* 0201-positive healthy individuals' peripheral blood 
      mononuclear cells (PBMC). Mature DCs were pulsed with synthesized peptides. 
      Autologous CD8(+) T cells from the HLA-A* 0201 healthy donor were stimulated with 
      the peptide-pulsed DCs as CTL. CTL activity was assessed by lactate dehydrogenase 
      release assay and IFN-gamma released by enzyme-linked immunospot assay. Pentamer was 
      synthesized for HLA-A* 0201 restricted epitope P1126, then was used to detect 
      specific CTL in PBMC of PDAC patients. RESULTS: Five candidate HLA-A*0201 
      epitopes were predicted, LLLGVGTFV (P1125) and LLGVGTFVV (P1126) were determined 
      as the two with more HLA-A*0201 affinity. Mature DCs could be induced from PBMCs. 
      CTL induced by peptide P1126 could lyses T2 cells pulsed with peptide P1126 and 
      HCT-116 cells [MUC4(+), HLA-A2(+)]. The number of CTL induced by peptide P1126 
      which could secret IFN-gamma (130.3 +/- 6.6) was obviously higher than that in the 
      negative group. By Pentamer assay, P1126-pentamer and CD8 double positive CTL 
      could be detected in PBMC of PDAC patients with MUC4(+) than patients with 
      MUC4(-), but no significant difference of CTL frequency between patients with 
      HLA-A2(+) and with HLA-A2(-) in MUC4(+) PDAC patients. CONCLUSIONS: Tumor 
      associated antigen MUC4-derived HLA-A* 0201-restrictive cytotoxic T lymphocyte 
      (CTL) epitope P1126 can induce CTL reaction. The CTL can secret immunologic 
      active material to induce the specific target cells lysis. P1126 epitope can be 
      naturally presented in PBMC of PDAC patients, but its HLA-restriction may not be 
      perfect.
FAU - Gao, Wen-tao
AU  - Gao WT
AD  - Center of Pancreatic Surgery, the First Affiliated Hospital with Nanjing Medical 
      University, China.
FAU - Zhang, Jing-jing
AU  - Zhang JJ
FAU - Zhu, Yi
AU  - Zhu Y
FAU - Wei, Ji-shu
AU  - Wei JS
FAU - Meng, Kai
AU  - Meng K
FAU - Chen, Jian-min
AU  - Chen JM
FAU - Wu, Jun-li
AU  - Wu JL
FAU - Miao, Yi
AU  - Miao Y
LA  - chi
PT  - English Abstract
PT  - Journal Article
PL  - China
TA  - Zhonghua Wai Ke Za Zhi
JT  - Zhonghua wai ke za zhi [Chinese journal of surgery]
JID - 0153611
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (MUC4 protein, human)
RN  - 0 (Mucin-4)
SB  - IM
MH  - Antigens, Neoplasm/*immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/immunology
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - HLA-A Antigens/immunology
MH  - HLA-A2 Antigen/immunology
MH  - Humans
MH  - Mucin-4/*immunology
MH  - Pancreatic Neoplasms/*immunology
MH  - T-Lymphocytes, Cytotoxic/immunology
EDAT- 2010/11/26 06:00
MHDA- 2011/08/24 06:00
CRDT- 2010/11/25 06:00
PHST- 2010/11/25 06:00 [entrez]
PHST- 2010/11/26 06:00 [pubmed]
PHST- 2011/08/24 06:00 [medline]
PST - ppublish
SO  - Zhonghua Wai Ke Za Zhi. 2010 Sep 15;48(18):1416-24.