IN-VIVO CROSS-PRIMING OF MHC CLASS-I - RESTRICTED ANTIGENS REQUIRES THE TAP TRANSPORTER

Recent in vitro evidence suggests two alternative mechanisms by which bone marrow-derived APCs may process exogenous antigens for presentati on to CTL in vivo, a phenomenon termed cross-priming. Although in vitr o studies have suggested that both TAP-dependent and TAP-independent p athways exist, we have now demonstrated an absolute requirement for a functional TAP for cross-priming to occur in vivo. Bone marrow chimera s reconstituted with marrow from TAP-defective donors develop function al CD8(+) CTL, but have APCs with disrupted TAP function. In such chim eras, in vivo priming of naive CTL was observed when antigen was targe ted to the ER in a TAP-independent fashion, but cross-priming could no t be demonstrated. These results support the TAP-dependent mechanism o f cross-priming.