DIFFERENTIAL REACTIVITY OF RESIDUAL CD8(-LYMPHOCYTES IN TAP1 AND BETA-2-MICROGLOBULIN MUTANT MICE() T)

TAP1 -/- and beta 2-microglobulin (beta 2m) -/- mice (H-2(b) backgroun d) express very low levels of major histocompatibility complex (MHC) c lass I molecules on the cell surface. Consequently these mice have low numbers of mature CD8(+) T lymphocytes. However, TAP1 -/- mice have s ignificantly higher numbers of CD8(+) T cells than beta 2m -/- mice. A lloreactive CD8(+) cytotoxic T lymphocyte (CTL) responses were also st ronger in TAP1 -/- mice than in beta 2m -/- mice. Alloreactive CTL gen erated in TAP1 -/- and beta 2m -/- mice cross-react with H-2(b)-expres sing cells. Surprisingly, such cross-reactivity was stronger with allo reactive CTL from beta 2m -/- mice than with similar cells from TAP1 - /- mice, The beta 2m -/- mice also responded more strongly when primed with and tested against cells expressing normal levels of H-2(b) MHC class I molecules. Such H-2(b)-reactive CD8(+) CTL from beta 2m -/- mi ce but not from TAP1 -/- mice also reacted with TAP1 -/- and TAP2-defi cient RMA-S cells. In contrast, H-2(b)-reactive CD8(+) CTL from neithe r beta 2m -/- mice nor TAP1 -/- mice killed beta 2m -/- cells. In line with these results, beta 2m -/- mice also responded when primed and t ested against TAP1 -/- cells. We conclude that the reactivity of resid ual CD8(+) T cells differs between TAP1 -/- and beta 2m -/- mice. The MHC class I-deficient phenotype of TAP1 -/- and beta 2m -/- mice is no t equivalent: class I expression differs between the two mouse lines w ith regard to quality as well as quantity. We propose that the differe nces observed in numbers of CD8(+) T cells, their: ability to react wi th alloantigens and their cross-reactivity with normal H-2(b) class I are caused by differences in the expression of MHC class I Ligands on selecting cells in the thymus.