MHC class I expression and CD8+ T cell development in TAP1/β2-microglobulin double mutant mice

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Abstract
We have bred to homozygosity gene disruptions for the transporter associated with antigen processing 1 (TAP1) and β2-microglobulin (β2m), each of which plays a distinct role in providing class I MHC subunits. Surface expression of H-2Kb or Db on cells derived from TAP1/β2m –/– mice was undetectable by immunofluorescence or immunoprecipitation, unlike the situation observed for TAP1 –/– and β2m –/– single mutant mice. Yet, TAP1/β2m –/– cells were able to elicit a CD8+cytotoxic T cell (CTL) response in mice of different H-2 haplotypes and could be killed by anti-H-2bspecific CTL. Furthermore, TAP1/β2m –/– skin grafts were rejected by bm1 mutant mice. This suggests that very low levels of conformed class I heavy chains can reach the cell surface even in the complete absence of TAP1 and β2m gene products, and that these molecules may select a functional CD8+ T cell repertoire. Indeed, CD4–CD8+ T cells were detected in TAP1/β2m –/– mice, but in numbers lower than in either of the single mutant mice. Nonetheless, it was possible to elicit a CD8+ allospecific and H-2b reactive CTL response in TAP1/β2m –/– mice. In line with this, TAP1/β2m –/– mice rapidly rejected TAP1/β2m –/– skin grafts. Our results suggest that some MHC class I heavy chains in TAP1/β2m –/– cells can reach the cell surface in a form that allows recognition by allospecific CTL and positive selection of CD8+ T cells.

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