Identification of a novel tumor-specific CTL epitope presented by RMA, EL-4, and MBL-2 lymphomas reveals their common origin.
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.
van Hall
T
T
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
van Bergen
J
J
van Veelen
P A
PA
Kraakman
M
M
Heukamp
L C
LC
Koning
F
F
Melief
C J
CJ
Ossendorp
F
F
Offringa
R
R
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D001665:Binding Sites / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000302:isolation & purification / Q000378:metabolism*; D005622:Friend murine leukemia virus; D005786:Gene Expression Regulation / Q000276:immunology; D019674:Genes, T-Cell Receptor beta; D007942:Leukemia, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008979:Moloney murine leukemia virus; D009842:Oligopeptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism; D011925:Rauscher Virus; D020539:Sequence Analysis, Protein; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D013945:Thymoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000637:transplantation; D014412:Tumor Virus Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D009842:Oligopeptides