Radiation leukemia virus-induced T-cell lymphomas with common T-cell receptor variable region structure and similar binding specificity for retrovirus.
The 5C2 cell line was derived following culture of mouse spleen cells exposed in vivo and in vitro to radiation leukemia virus (RadLV) containing supernatants from the C6VL/1 T cell lymphoma. This cell line has been found to express an alpha beta T-cell receptor (TCR) identifiable with the Mab124-40 anti-clonotypic antibody which is specific for C6VL/1. It has been shown to be genetically and phenotypically distinct from C6VL/1 with a unique phenotype, i.e. CD4-, CD8-, CD3+, TCR-alpha beta. 5C2 has been shown to express high levels of alpha and beta chain mRNA and to utilize the same or similar V alpha and V beta region genes as C6VL/1. Whereas C6VL/1 binds cross-reactively to both RadLV/C6VL and an unrelated isolate RadLV/VL3, 5C2 has binding specificity for only RadLV/C6VL, which induced its proliferation. The anti-clonotypic antibody Mab124-40 specifically and completely inhibits binding of 5C2 to RadLV/C6VL at concentrations as low as 300 ng/ml. The 5C2 cell line can also be stimulated to increased proliferation by RadLV/C6VL. All of these data are consistent with the role of a TCR alpha beta heterodimer in binding and stimulation by RadLV and satisfy one prediction of the receptor-mediated leukemogenesis hypothesis that T-cell clones identifiable by their T-cell receptor clonotype may be targets for transformation by a particular retrovirus.
O'Neill
H C
HC
Developmental Haematology Group, John Curtin School of Medical Research, Australian National University, Canberra.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015152:Blotting, Northern; D002460:Cell Line; D015342:DNA Probes; D016399:Lymphoma, T-Cell / Q000209:etiology* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D016721:Radiation Leukemia Virus; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D012190:Retroviridae; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D015342:DNA Probes; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell