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.