Positive selection of self- and alloreactive CD8+ T cells in Tap-1 mutant mice

Abstract

Mice with a homozygous deletion in their Tap-1 gene (-/- mice) express very low levels of cell membrane major histocompatibility complex class I molecules and have <1% peripheral CD8+ T cells. We show that these -/- mice but not their +/- littermates display strong primary syngeneic anti-H-2Kb and -Db-specific responses mediated by CD8+ T cells. These responses are augmented by in vivo priming. Further, -/- mice primed in vivo with H-2(d) alloantigens generate an anti-H-2(d) response which appears nearly as strong as that found in +/- littermates. Both -/- anti-H-2b and anti-H-2(d) T cells do not recognize target cells from Tap-1 -/- animals or Tap-2-deficient RMA- S cells. Thus, some CD8+ anti-self and alloreactive T cells can be selected in the absence of Tap proteins.