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Updated: Oct 15, 2026
Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus
Published on: March 8, 2012
Identification of a novel tumor-specific CTL epitope presented by RMA, EL-4, and MBL-2 lymphomas reveals their common
T van Hall1, J van Bergen, P A van Veelen
1Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Abstract:
C57BL/6 mice generate a vigorous H-2Db-restricted CTL response against murine leukemia virus (MuLV)-induced tumors. For many years it has been suggested that this response is directed to an MuLV-encoded peptide as well as to a nonviral tumor-associated peptide. Recently, a peptide from the leader sequence of gag was demonstrated to be the MuLV-derived epitope. Here we describe the molecular identification of the tumor-associated epitope. Furthermore, we show that the CTL response against this epitope can restrict the outgrowth of MuLV-induced tumors in vivo. The epitope is selectively presented by the MuLV-induced T cell tumors RBL-5, RMA, and MBL-2 as well as by the chemically induced T cell lymphoma EL-4. Intriguingly, these tumors share expression of the newly identified epitope because they represent variants of the same clonal tumor cell line, as evident from sequencing of the TCR alpha- and beta-chains, which proved to be identical. Our research shows that all sources of RBL-5, RMA, RMA-S, MBL-2, and EL-4 tumors are derived from a single tumor line, most likely EL-4.
Insights
Researchers identified a novel tumor-associated epitope in C57BL/6 mice, crucial for controlling murine leukemia virus (MuLV)-induced tumors. This finding advances understanding of anti-tumor immunity and epitope-based therapies.
Area of Science:
- Immunology
- Oncology
- Virology
Background:
- C57BL/6 mice mount a strong cytotoxic T lymphocyte (CTL) response against murine leukemia virus (MuLV)-induced tumors.
- This response targets both viral and non-viral tumor-associated peptides.
- A viral epitope from the gag leader sequence was previously identified.
Purpose of the Study:
- To identify the molecular basis of the non-viral tumor-associated epitope.
- To investigate the role of this epitope in anti-tumor immunity in vivo.
- To determine the origin of commonly used MuLV-induced tumor cell lines.
Main Methods:
- Molecular identification of tumor-associated epitopes.
- In vivo studies assessing CTL response and tumor outgrowth.
- T-cell receptor (TCR) alpha- and beta-chain sequencing.
Main Results:
- The molecular identity of the tumor-associated epitope was determined.
- CTL responses targeting this epitope were shown to restrict tumor outgrowth in vivo.
- Analysis revealed that RBL-5, RMA, MBL-2, and EL-4 tumor lines are variants of a single clonal line, likely EL-4, sharing the identified epitope.
Conclusions:
- The identified tumor-associated epitope is a key target for CTL-mediated anti-tumor immunity.
- This epitope's presence in multiple tumor lines, originating from a single source, has implications for immunotherapy development.
- Understanding shared tumor epitopes can inform strategies for broader therapeutic application.
