We describe mice that express a transgenic T cell receptor alpha/beta (TCR-alpha/beta) specific for peptide 111-119 from influenza hemagglutinin presented by I-Ed class II major histocompatibility complex (MHC) molecules. The transgenic TCR is expressed on CD4+8- as well as CD4-8+ mature T cells even in mice that are deficient in rearrangement or do not express endogenous TCR-alpha genes. The CD4-8+ T cells require I-Ed class II MHC molecules for positive selection and can be activated to proliferate and to kill by I-Ed molecules presenting the relevant peptide. Full maturation of these cells, however, also requires the presence of class I MHC molecules. The results are compatible with the notion that T cell maturation requires multiple receptor-ligand interactions and establish an exception to the rule that class II-restricted TCRs are exclusively expressed by mature CD4+8- cells.