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 presentation to CTL in vivo, a phenomenon termed cross-priming. Although in vitro studies have suggested that both TAP-dependent and TAP-independent pathways exist, we have now demonstrated an absolute requirement for a functional TAP for cross-priming to occur in vivo. Bone marrow chimeras reconstituted with marrow from TAP-defective donors develop functional CD8+ CTL, but have APCs with disrupted TAP function. In such chimeras, in vivo priming of naive CTL was observed when antigen was targeted to the ER in a TAP-independent fashion, but cross-priming could not be demonstrated. These results support the TAP-dependent mechanism of cross-priming.
Huang
A Y
AY
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Bruce
A T
AT
Pardoll
D M
DM
Levitsky
H I
HI
D018528:ATP-Binding Cassette Transporters / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation; D005260:Female; D006183:H-2 Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D011828:Radiation Chimera / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D018528:ATP-Binding Cassette Transporters; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I