Beschreibung:
<jats:title>Abstract</jats:title><jats:p>The response of H-Y-specific TCR-transgenic CD8+ T cells to Ag is characterized by poor proliferation, cytolytic activity, and IFN-γ secretion. IFN-γ secretion, but not cytotoxic function, can be rescued by the B7.1 molecule, suggesting that costimulation can selectively enhance some, but not all, effector CD8+ T cell responses. Although the H-Y epitope binds H-2Db relatively less well than some other epitopes, it can induce potent CTL responses in nontransgenic mice, suggesting that the observed poor responsiveness of transgenic CD8+ T cells cannot be ascribed to the epitope itself. Previously reported reactivity of this TCR to H-2Ab is also not the cause of the poor responsiveness of the H-Y-specific CD8+ T cells, as H-Y-specific CD8+ T cells obtained from genetic backgrounds lacking H-2Ab also responded poorly. Rather, reducing the levels of H-2b class I molecules by breeding the mice to (C57BL/6 × B10.D2)F1 or TAP1+/− backgrounds partially restored cytotoxic activity and enhanced proliferative responses. These findings demonstrate that the self MHC class I gene dosage may regulate the extent of CD8+ T cell responsiveness to Ag.</jats:p>