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Differential reactivity of residual CD8+ T lymphocytes in TAP1 and beta 2-microglobulin mutant mice.

Ljunggren HG, Van Kaer L, Ashton-Rickardt PG, Tonegawa S, Ploegh HL
Eur J Immunol. 1995 25 (1): 174-8

PMID: 7843229 · DOI:10.1002/eji.1830250129

TAP1 -/- and beta 2-microglobulin (beta 2m) -/- 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 beta 2m -/- mice. Alloreactive CD8+ cytotoxic T lymphocyte (CTL) responses were also stronger in TAP1 -/- mice than in beta 2m -/- mice. Alloreactive CTL generated in TAP1 -/- and beta 2m -/- mice cross-react with H-2b-expressing cells. Surprisingly, such cross-reactivity was stronger with alloreactive 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-2b MHC class I molecules. Such H-2b-reactive CD8+ CTL from beta 2m -/- 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 beta 2m -/- mice nor TAP1 -/- mice killed beta 2m -/- cells. In line with these results, beta 2m -/- mice also responded when primed and tested against TAP1 -/- cells. We conclude that the reactivity of residual CD8+ T cells differs between TAP1 -/- and beta 2m -/- mice. The MHC class I-deficient phenotype of TAP1 -/- and beta 2m -/- 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.

MeSH Terms (14)

Animals ATP-Binding Cassette Transporters ATP Binding Cassette Transporter, Subfamily B, Member 2 beta 2-Microglobulin Cell Line Cytotoxicity Tests, Immunologic Flow Cytometry H-2 Antigens Isoantigens Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Mutant Strains T-Lymphocytes, Cytotoxic

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