T cells with two Tcrbeta chains and reactivity to both MHC/idiotypic peptide and superantigen

It is thought that Tcrbeta genes are effectively allelically excluded, while Tcralpha genes are not. We report here that endogenous Tcrbeta genes are expressed on as much as 5-7% of CD4+ T cells in 8-week-old Tcralphabeta-transgenic mice. In this model, the transgenic Tcr recognizes residues 91 - 101 of a lambda2(315) Ig light chain, presented on the I-Ed class II molecule. From such mice, a CD4+ T cell clone was isolated which not only responded to lambda2(315), but also mobilized Ca2+ and proliferated in response to Mls-1a. (Inadvertently we found that the C3H/Tif substrain, in contrast to C3H/HeJ, is Mls-1a positive.) The clone expressed the transgenic Tcr (Valpha1 and Vbeta8.2), and in addition an endogenous Vbeta6 chain, conferring the Mls-1a reactivity. On the population level, 1-2% of Tcr-transgenic lymph node cells displayed Vbeta6, in addition to the transgenic beta-chain. Such dual Tcrbeta expressor cells could be preferentially expanded in vitro by first stimulating with DBA/2 spleen cells and then with lambda2(315)-pulsed BALB/c antigen-presenting cells. In addition to demonstrating that allelic exclusion of Tcrbeta-chain genes is substantial but not complete in this model, the data show that the double 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 for both early (Ca2+ mobilization) and late (proliferation) T cells activation parameters. Dual Tcr cells may have a role in the pathogenesis of autoimmune diseases: If naive T cells are first stimulated by (infectious) superantigen, they could later, as activated T cells, respond to self-peptide/MHC on costimulation-deficient cells and cause autoimmunity. As a corollary, dual Tcr Id-specific T cells could, once activated, directly regulate Id+ B cells.