Differential reactivity of residual CD8+ T lymphocytes in TAP1 and beta 2-microglobulin mutant mice.
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.
Ljunggren
H G
HG
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139-4307.
Van Kaer
L
L
Ashton-Rickardt
P G
PG
Tonegawa
S
S
Ploegh
H L
HL
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000235:genetics / Q000502:physiology*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D006183:H-2 Antigens; D007519:Isoantigens; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D001613:beta 2-Microglobulin