T-CELLS WITH 2 TCR-BETA CHAINS AND REACTIVITY TO BOTH MHC IDIOTYPIC PEPTIDE AND SUPERANTIGEN/

It is thought that Tcr beta genes are effectively allelically excluded , while Tcr alpha genes are not. We report here that endogenous Tcr be ta genes are expressed on as much as 5-7% of CD4(+) T cells in 8-week- old Tcr alpha beta-transgenic mice. In this model, the transgenic Tcr recognizes residues 91-101 of a lambda 2(315) Ig light chain, presente d on the I-Ed class II molecule. From such mice, a CD4(+) T cell clone was isolated which not only responded to lambda 2(315), but also mobi lized Ca2+ and proliferated in response to lambda 2(315). (Inadvertent ly we found that the C3H/Tif substrain, in contrast to C3H/HeJ, is Mls -1(a) positive,) The clone expressed the transgenic Tcr (V alpha 1 and V beta 8.2), and in addition an endogenous V beta 6 chain, conferring the Mls-1(a) reactivity. On the population level, 1-2% of Tcr-transge nic lymph node cells displayed V beta 6, in addition to the transgenic beta-chain. Such dual Tcr beta expressor cells could be preferentiall y expanded in vitro by first stimulating with DBA/2 spleen cells and t hen with lambda 2(315)-pulsed BALB/c antigen-presenting cells. In addi tion to demonstrating that allelic exclusion of Tcr beta-chain genes i s substantial but not complete in this model, the data show that the d ouble beta-chain expressors can have two different specificities, and be signaled through both receptors, by physiological ligands. However, such dual-Tcr T cells appear to have reduced sensitivity to ligands, due to their decreased expression of each receptor. This holds true fo r both early (Ca2+ mobilization) and late (proliferation) T cells acti vation parameters. Dual Tcr cells may have a role in the pathogenesis of autoimmune diseases: If naive T cells are first stimulated by (infe ctious) superantigen, they could later, as activated T cells, respond to self-peptide/MHC on costimulation-deficient cells and cause autoimm unity. Asa corollary, dual Tcr Id-specific T cells could, once activat ed, directly regulate Id(+) B cells. (C) 1996 Academic Press, Inc.