Skewed T-cell receptor Vbeta8.2 expression in transgenic CD2-myc induced thymic lymphoma: a role for antigen stimulation in tumour development?
Transgenic mice expressing the c-myc proto-oncogene under the control of the CD2-dominant control region show stochastic development of mainly clonal thymic lymphoma with long latency, indicating that cooperative events are needed for the development of the fully malignant phenotype. Previous studies have suggested that T-cell receptor-associated signals can contribute to tumour development. We have therefore used this transgenic model of T-cell transformation to determine whether antigen-specific responses could constitute an epigenetic event in lymphomagenesis. The T-cell receptor (TcR) repertoires of lymphoma clones were analysed with a panel of monoclonal antibodies (Abs) recognizing TcR Vbeta chains. The Vbeta repertoire of tumour clones arising in these mice was non-random with overrepresentation of Vbeta8.2 TcR species. The majority of Vbeta8.2+ clones were of a mature CD3+ CD8 single-positive (SP) phenotype. The biased TcR usage, together with a mature cell phenotype is consistent with the hypothesis that TcR-mediated signals cooperate with activated myc during T-cell transformation.
Webster
G
G
Department of Veterinary Pathology, University of Glasgow Veterinary School, UK.
Onions
D E
DE
Neil
J C
JC
Cameron
E R
ER
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D016259:Genes, myc; D016130:Immunophenotyping; D008223:Lymphoma / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D015398:Signal Transduction; D013953:Thymus Neoplasms / Q000378:metabolism*
D000945:Antigens, Differentiation, T-Lymphocyte; D016693:Receptors, Antigen, T-Cell, alpha-beta