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

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Abstract
TAP1 ‐/‐ and β2‐microglobulin (β2m) ‐/‐ mice (H‐2b 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‐2b‐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‐2b MHC class I molecules. Such H‐2b‐reactive CD8+ CTL from β2m ‐/‐ mice but not from TAP1 ‐/‐ mice also reacted with TAP1 ‐/‐ and TAP2‐deficient RMA‐S cells. In contrast, H‐2b‐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‐2b class I are caused by differences in the expression of MHC class I ligands on selecting cells in the thymus.