Differential reactivity of residual CD8 + T lymphocytes in TAP1 and β2‐microglobulin mutant mice

Abstract TAP1 ‐/‐ and β2‐microglobulin (β2m) ‐/‐ mice (H‐2 b background) express very low levels of major histocompatibility complex (MHC) class I molecules on the cell surface. Consequently these mice have low numbers of mature CD8 + T lymphocytes. However, TAP1 ‐/‐ mice have significantly higher numbers of CD8 + T cells than β2m ‐/‐ mice. Alloreactive CD8 + cytotoxic T lymphocyte (CTL) responses were also stronger in TAP1 ‐/‐ mice than in β2m ‐/‐ mice. Alloreactive CTL generated in TAP1 ‐/‐ and β2m ‐/‐ mice cross‐react with H‐2 b ‐expressing cells. Surprisingly, such cross‐reactivity was stronger with alloreactive CTL from β2m ‐/‐ mice than with similar cells from TAP1 ‐/‐ mice. The β2m ‐/‐ 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 β2m ‐/‐ mice but not from TAP1 ‐/‐ mice also reacted with TAP1 ‐/‐ and TAP2‐deficient RMA‐S cells. In contrast, H‐2 b ‐reactive CD8 + CTL from neither β2m ‐/‐ mice nor TAP1 ‐/‐ mice killed β2m ‐/‐ cells. In line with these results, β2m ‐/‐ mice also responded when primed and tested against TAP1 ‐/‐ cells. We conclude that the reactivity of residual CD8 + T cells differs between TAP1 ‐/‐ and β2m ‐/‐ mice. The MHC class I‐deficient phenotype of TAP1 ‐/‐ and β2m ‐/‐ mice is not equivalent: class I expression differs between the two mouse lines with regard to quality as well as quantity. We propose that the differences observed in numbers of CD8 + T cells, their ability to react with 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.