Identification of a novel tumor-specific CTL epitope presented by RMA, EL-4, and MBL-2 lymphomas reveals their common origin

T van Hall, J van Bergen, PA van Veelen… - The Journal of …, 2000 - journals.aai.org
T van Hall, J van Bergen, PA van Veelen, M Kraakman, LC Heukamp, F Koning, CJM Melief
The Journal of Immunology, 2000journals.aai.org
C57BL/6 mice generate a vigorous H-2D b-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 …
Abstract
C57BL/6 mice generate a vigorous H-2D b-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 α-and β-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.
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