POSITIVE AND NEGATIVE SELECTION IN TRANSGENIC MICE EXPRESSING A T-CELL RECEPTOR-SPECIFIC FOR INFLUENZA NUCLEOPROTEIN AND ENDOGENOUS SUPERANTIGEN

A transgenic mouse was generated expressing on most (>80%) of thymocyt es and peripheral T cells a T-cell receptor isolated from a cytotoxic T-cell clone (F5), This clone is CD8+ and recognizes alphaalpha366-374 of the nucleoprotein (NP 366-374) of influenza virus (A/NT/60/68), in the context of Class I MHC D(b) (Townsend et al., 1986). The receptor utilizes the Vbeta11 and Valpha4 gene segments for the beta chain and alpha chain, respectively (Palmer et al., 1989). The usage of Vbeta11 makes this TcR reactive to Class II IE molecules and an endogenous li gand recently identified as a product of the endogenous mammary tumour viruses (Mtv) 8, 9, and 11 (Dyson et al., 1991). Here we report the d evelopment of F5 transgenic T cells and their function in mice of the appropriate MHC (C57BL/10 H-2b, IE-) or in mice expressing Class II MH C IE (e.g., CBA/Ca H-2K and BALB/c H-2d) and the endogenous Mtv ligand s. Positive selection of CD8+ T cells expressing the Vbeta11 is seen i n C57BL/10 transgenic mice (H-2b). Peripheral T cells from these mice are capable of killing target cells in an antigen-dependent manner aft er a period of in vitro culture with IL-2. In the presence of Class II MHC IE molecules and the endogenous Mtv ligand, most of the single-po sitive cells carrying the transgenic T-cell receptor are absent in the thymus. Unexpectedly, CD8+ peripheral T-cells in these (H-2k or H-2d) F5 mice are predominantly Vbeta11 positive and also have the capacity to kill targets in an antigen-dependent manner. This is true even fol lowing backcrossing of the F5 TcR transgene to H-2d scid/scid mice, in which functional rearrangement of endogenous TcR alpha- and beta-chai n genes is impaired.