Negative trans-regulation of T-cell antigen receptor/T3 complex mRNA expression in murine T-lymphoma somatic cell hybrids.
The antigen-specific T-cell receptor (TCR) is composed of variable antigen-recognition chains TCR-alpha and TCR-beta in noncovalent association with the invariant T3 multimer. The TCR-alpha and TCR-beta chains are encoded by gene segments that must be juxtaposed by rearrangement in order to be expressed. To examine whether mechanisms other than gene rearrangement might regulate TCR/T3 gene expression, somatic cell hybrids were formed among closely related murine SL12 T-lymphoma clones that differ in TCR/T3 mRNA levels. In hybrid cells formed between cell clones in which one parent is TCR-beta+ and the other is TCR-beta-, the resultant hybrid cells lack detectable TCR-beta transcripts. Since the protein synthesis inhibitor cycloheximide partially reverses TCR-beta repression in the hybrid cells, we postulate that a labile repressor protein is involved. The amount of mRNA encoding one of the T3 polypeptide chains, T3-delta, is also strongly negatively transregulated in the same hybrid cells in which TCR-beta mRNA expression is repressed. The negative trans-regulation of TCR-beta and T3-delta mRNA expression is relatively specific, since the levels of TCR-alpha mRNA and several thymocyte surface antigens are not repressed in somatic cell hybrids. Our results indicate that rearrangement of the TCR genes alone is not sufficient for TCR-beta expression and that trans-acting factors regulate the amounts of both TCR-beta and T3-delta mRNA in this system.
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000235:genetics*; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D005786:Gene Expression Regulation; D006822:Hybrid Cells; D008223:Lymphoma / Q000276:immunology*; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D014158:Transcription, Genetic
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D003513:Cycloheximide