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 vivo involves the transfer to host APCs of heat shock protein glycoprotein 96-chaperoned antigenic peptides released from the endoplasmic reticulum (ER) of dying or infected cells. We have tested this possibility directly using TAP-deficient cell lines lacking antigenic ER peptides derived from two model Ags, the human adenovirus type 5 early regions E1A and E1B. Although both proteins were well expressed, the cells were not recognized by E1A- or E1B-specific CTLs unless the relevant epitope was either provided exogenously as a synthetic peptide or targeted to the ER in a TAP-independent fashion. Despite the absence of these ER peptides, the TAP1-/- cells were able to efficiently cross-prime E1A- and E1B-specific CTLs following immunization of syngeneic mice. These results indicate that, although purified peptide/glycoprotein 96 complexes are potent immunogens, the mechanism of CTL cross-priming in vivo does not depend upon antigenic peptides in the ER of immunizing cells.
Department of Immunohematology and Blood Bank, University Hospital Leiden, The Netherlands. sps@liai.org
S P
SP
Schoenberger
E I
EI
van der Voort
G M
GM
Krietemeijer
R
R
Offringa
C J
CJ
Melief
R E
RE
Toes
D017500:Adenovirus E1A Proteins / Q000276:immunology; D017501:Adenovirus E1B Proteins / Q000276:immunology; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004721:Endoplasmic Reticulum / Q000276:immunology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000648:ultrastructure
D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins; D000951:Antigens, Neoplasm; D000956:Antigens, Viral; C052646:sarcoma glycoprotein gp96 rejection antigens