PMID- 19087545
OWN - NLM
STAT- MEDLINE
DCOM- 20111028
LR  - 20081217
IS  - 0529-567X (Print)
IS  - 0529-567X (Linking)
VI  - 43
IP  - 10
DP  - 2008 Oct
TI  - [Identification of T cell epitopes from ovarian cancer associated anti-idiotype 
      antibody].
PG  - 764-9
AB  - OBJECTIVE: To identify the T cell epitopes from ovarian cancer associated 
      anti-idiotypic antibody 6B11 in order to explore the molecular basis of 6B11 
      induced cellular immune responses against ovarian cancer. METHODS: Potential 
      human leukocyte antigen (HLA) A0201 ligands were predicted by using SYFPEITHI 
      algorithm and tested by the T2 binding assay for screening of HLA-A2 binding 
      peptides from 6B11 complimentary determining region (CDR). Cytotoxic T 
      lymphocytes (CTL) to 6B11 or peptides were generated by 3 rounds of in vitro 
      stimulation with 6B11 or peptide-pulsed dendritic cells (DC), and then tested by 
      (51)Cr-release assay to ascertain the CTL epitope of 6B11. Cell proliferation 
      assay was performed by using 6B11 specific CTL as responder cells and 
      peptide-pulsed DC as stimulators to ascertain the helper T lymphocyte (Th) 
      epitope of 6B11. Cytokine assay and interferon-gamma ELISPOT assay were performed 
      to verify the CTL and Th epitope of 6B11 further. RESULTS: Light chain CDR3 
      peptide (VL CDR3) of 6B11 induced specific CTL to kill HLA-A2 and target antigen 
      positive ovarian cancer cells, which could be blocked by anti human major 
      histocompatibility complex (MHC) I antibody. Heavy chain CDR3 peptide (VH CDR3) 
      of 6B11 stimulated the proliferation of 6B11-primed CTL, which could be blocked 
      mainly by anti human MHC-II antibody, and further experiments showed that part of 
      the VH CDR3 peptide-primed CTL killed K562 cells. Peptides in VL CDR3 and VH CDR3 
      were the CTL and Th epitope mimicking the original antigen of 6B11 respectively. 
      Collaboration of 6B11 CTL and Th epitope, or 6B11 CTL epitope and keyhole limpet 
      hemocyanin (KLH), the former was more powerful in inducing specific cellular 
      immune responses against ovarian cancer. 6B11 or corresponding CTL and Th epitope 
      specific CTL secreted high levels of interleukin-2 (1630, 1503 ng/L) and 
      interferon-gamma (5620, 5421 ng/L), while basal level of interleukin-4 was 
      detected (253, 274 ng/L). ELISPOT assay confirmed the existence of specific 
      interferon-gamma secreting cells in 6B11 or epitopes specific CTL (196/1 x 10(6) 
      T cell, 184/1 x 10(6) T cell). CONCLUSIONS: VL CDR3 and VH CDR3 peptides of 6B11 
      are the CTL and Th epitopes mimicking original antigen which could duplicate the 
      activity of intact 6B11 to induce the cellular immune responses against ovarian 
      cancer. The results have significant theoretical and practical value in 
      application of anti-idiotypic antibody as anti tumor vaccine. The acquired CTL 
      and Th epitopes as constituents of future multiple peptides against ovarian 
      cancer could be used in peptide vaccine based ovarian cancer therapy.
FAU - Li, Wei
AU  - Li W
AD  - Department of Gynecologic Oncology Center, Peking University People's Hospital, 
      Beijing 100044, China.
FAU - Cui, Heng
AU  - Cui H
FAU - Chang, Xiao-Hong
AU  - Chang XH
FAU - Cheng, Hong-Yan
AU  - Cheng HY
FAU - Cheng, Ye-Xia
AU  - Cheng YX
FAU - Feng, Jie
AU  - Feng J
FAU - Fu, Tian-Yun
AU  - Fu TY
LA  - chi
PT  - English Abstract
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Zhonghua Fu Chan Ke Za Zhi
JT  - Zhonghua fu chan ke za zhi
JID - 16210370R
RN  - 0 (Antibodies, Anti-Idiotypic)
RN  - 0 (Antibodies, Neoplasm)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Complementarity Determining Regions)
RN  - 0 (Epitopes, T-Lymphocyte)
SB  - IM
MH  - Antibodies, Anti-Idiotypic/*immunology/pharmacology
MH  - Antibodies, Neoplasm/immunology
MH  - Antigens, Neoplasm/*immunology/metabolism
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Complementarity Determining Regions/immunology
MH  - Dendritic Cells/*immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Female
MH  - Humans
MH  - Ovarian Neoplasms/*immunology/therapy
MH  - T-Lymphocytes, Cytotoxic/*immunology
EDAT- 2008/12/18 09:00
MHDA- 2011/10/29 06:00
CRDT- 2008/12/18 09:00
PHST- 2008/12/18 09:00 [entrez]
PHST- 2008/12/18 09:00 [pubmed]
PHST- 2011/10/29 06:00 [medline]
PST - ppublish
SO  - Zhonghua Fu Chan Ke Za Zhi. 2008 Oct;43(10):764-9.