Bc. Giltorregrosa et al., MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I VIRAL-ANTIGEN PROCESSING IN THE SECRETORY PATHWAY DEFINED BY THE TRANS-GOLGI NETWORK PROTEASE FURIN, The Journal of experimental medicine, 188(6), 1998, pp. 1105-1116
Classical antigen presentation by major histocompatibility complex cla
ss I molecules involves cytosolic processing of endogenously synthesiz
ed antigens by proteasomes and translocation of processed peptides int
o the endoplasmic reticulum (ER) by transporters associated with antig
en presentation (TAP). Alternative pathways for processing of endogeno
us antigens, generally involving the ER, have been suggested but not f
ully proved. We analyzed the potential for class I presentation of pro
teolytic maturation of secretory antigens in the exocytic pathway. We
found that hepatitis B (HB) virus secretory core protein HBe can effic
iently deliver COOH-terminally located antigenic peptides for endogeno
us class I loading in the absence of TAP. Antigen presentation to spec
ific cytotoxic T lymphocytes correlates with protein maturation at the
COOH terminus, since modification of maturation and transport of HBe
through the secretory pathway alters antigen presentation. Both matura
tion and a necessary processing step occur in the Golgi or post-Golgi
compartment. Antigen presentation is independent of proteasome activit
y, but inhibitors of the trans-Golgi network resident protease furin i
nhibit both HBe maturation and antigen presentation. These results def
ine a new antigen processing pathway located in the secretory route, w
ith a central role for proteolytic maturation mediated by the subtilis
in protease family member furin as an efficient source for antigen pre
sentation.