CUTTING EDGE - CROSS-PRIMING OF CTL RESPONSES IN-VIVO DOES NOT REQUIRE ANTIGENIC PEPTIDES IN THE ENDOPLASMIC-RETICULUM OF IMMUNIZING CELLS

It has been proposed that the cross-priming of CTL responses in viva i nvolves the transfer to host APCs of heat shock protein glycoprotein 9 6-chaperoned antigenic peptides released from the endoplasmic reticulu m (ER) of dying or infected cells, We have tested this possibility dir ectly easing TAP-deficient cell lines lacking antigenic ER peptides de rived from two model Ags; the human adenovirus type 5 early regions E1 A and E1B, Although both proteins were well expressed, the cells were not recognized by E1A- or E1B-specific CTLs unless the relevant epitop e was either provided exogenously as a synthetic peptide or targeted t o the ER in a TAP-independent fashion. Despite the absence of these ER peptides, the TAP1(-/-) cells were able to efficiently cross-prime E1 A- and E1B-specific CTLs following immunization of syngeneic mice. The se results indicate that, although purified peptide/glycoprotein 96 co mplexes are potent immunogens, the mechanism of CTL cross-priming in v ivo does not depend upon antigenic peptides in the ER of immunizing ce lls.