Related Experiment Video
Updated: Jul 18, 2026
Detection of Human Leukocyte Antigen Biomarkers in Breast Cancer Utilizing Label-free Biosensor Technology
Published on: March 24, 2015
Identification of an HLA-A*0201 restricted Bcl2-derived epitope expressed on tumors
Mingjun Wang1, Britta Johansen, Mogens H Nissen
1Laboratory of Cellular Immunology, Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen N, Denmark.
Abstract:
A large number of human tumor-associated antigen-derived peptides have been identified that are recognized by CTLs in a MHC-I restricted fashion. The apoptosis inhibitory protein Bcl2 is overexpressed in many human cancers as part of their neoplastic phenotype. Since inhibition or loss of Bcl2 expression might impair tumor growth and survival, this protein may serve as a rational target for vaccine-induced CTL responses. By Western blot technique, we screened a panel of established human tumor cell lines for proteins involved in the apoptotic process. Two of eight tumor cell lines, a B lymphoma (Loukes) and a colon carcinoma (CCL220) cell line showed increased Bcl2 protein expression whereas the majority of tumor cell lines expressed proapoptotic proteins. Neither fibroblasts nor peripheral blood mononuclear cells showed Bcl2 expression. An HLA-A*0201 restricted CTL epitope was deduced in silica from the amino acid sequence of the Bcl2 protein and its binding affinity for HLA-A*0201 was confirmed using a biochemical binding assay. We here demonstrate that the 9-mer peptide Bcl2(85-93) induces specific CTL reactivity in immunized C57-A2K(b) or -A2D(b) tg mice. These Bcl2(85-93) specific CTLs react with and lyse Bcl2-expressing human colon carcinoma CCL220 cells which have been transfected with a chimeric HLA-A*0201/H2-K(b) DNA construct similar to that expressed in the transgenic mice. Based on these observations, we suggest that Bcl2(85-93) may be a target for immune therapy.
Insights
This study identifies the Bcl2(85-93) peptide as a potential target for cancer immunotherapy. Specific cytotoxic T lymphocytes (CTLs) targeting this peptide can effectively eliminate Bcl2-expressing tumor cells, suggesting a new avenue for cancer vaccines.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Overexpression of the apoptosis inhibitory protein Bcl2 is common in human cancers, contributing to tumor growth and survival.
- Bcl2 can be a potential target for vaccine-induced cytotoxic T lymphocyte (CTL) responses.
- Identifying tumor-specific antigens is crucial for developing effective cancer immunotherapies.
Purpose of the Study:
- To investigate Bcl2 as a potential target for cancer immunotherapy.
- To identify and characterize CTL responses against Bcl2-derived peptides.
- To evaluate the efficacy of Bcl2-specific CTLs in targeting cancer cells.
Main Methods:
- Screened human tumor cell lines for Bcl2 protein expression using Western blot.
- Deduced and synthesized an HLA-A*0201 restricted CTL epitope from the Bcl2 protein sequence.
- Confirmed peptide binding affinity to HLA-A*0201 using biochemical assays.
- Induced and analyzed Bcl2(85-93) specific CTL reactivity in transgenic mice.
- Assessed the ability of Bcl2-specific CTLs to lyse Bcl2-expressing tumor cells.
Main Results:
- Increased Bcl2 protein expression was observed in two of eight tested tumor cell lines (B lymphoma and colon carcinoma).
- Fibroblasts and peripheral blood mononuclear cells did not express Bcl2.
- The Bcl2(85-93) peptide was identified as an HLA-A*0201 restricted CTL epitope.
- Bcl2(85-93) specific CTLs were successfully induced in transgenic mice.
- These CTLs demonstrated specific reactivity and lysis of Bcl2-expressing colon carcinoma cells.
Conclusions:
- The Bcl2(85-93) peptide is a promising candidate for cancer immunotherapy.
- Targeting Bcl2 with specific CTLs offers a potential strategy for eliminating cancer cells.
- Further research into Bcl2-based cancer vaccines is warranted.
More Related Videos
Related Concept Videos
01:26Antigens Involved in Adaptive Immunity
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
01:22T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...