title: T cells with two Tcrbeta chains and reactivity to both MHC/idiotypic peptide and superantigen.
abstract: 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.
authors.affiliation: Institute of Immunology and Rheumatology, University of Oslo, Oslo, Norway.
authors.forename: L A
authors.initials: LA
authors.lastname: Munthe
authors.forename: E
authors.initials: E
authors.lastname: Blichfeldt
authors.forename: A
authors.initials: A
authors.lastname: Sollien
authors.forename: Z
authors.initials: Z
authors.lastname: Dembic
authors.forename: B
authors.initials: B
authors.lastname: Bogen
mesh_terms: D000818:Animals; D002999:Clone Cells; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D016513:Mice, SCID; D008822:Mice, Transgenic; D016744:Minor Lymphocyte Stimulatory Loci; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D018089:Superantigens / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C081278:T cell receptor Vbeta6.7a, human