Open AccessTargeting and retention of HPV16 E7 to the endoplasmic reticulum enhances immune tumour protection
Author(s) -
LoeraArias M.J.,
MartínezPérez A.G.,
BarreraHernández A.,
IbarraObregón E.R.,
GonzálezSaldívar G.,
MartínezOrtega J.I.,
RosasTaraco A.,
VillanuevaOlivo A.,
EsparzaGonzález S.C.,
VillatoroHernandez J.,
SaucedoCárdenas O.,
MontesdeOcaLuna R.
Publication year - 2010
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2009.00934.x
Subject(s) - kdel , endoplasmic reticulum , calreticulin , antigen , biology , epitope , immune system , er retention , calnexin , mhc class i , major histocompatibility complex , microbiology and biotechnology , virology , immunology , biochemistry , gene , mutant , golgi apparatus
The endoplasmic reticulum (ER) is where the major histocompatibility complex (MHC) class I molecules are loaded with epitopes to cause an immune cellular response. Most of the protein antigens are degraded in the cytoplasm to amino acids and few epitopes reach the ER. Antigen targeting of this organelle by Calreticulin (CRT) fusion avoids this degradation and enhances the immune response. We constructed a recombinant adenovirus to express the E7 antigen with an ER‐targeting signal peptide (SP) plus an ER retention signal (KDEL sequence). In cell‐culture experiments we demonstrated that this new E7 antigen, SP‐E7‐KDEL, targeted the ER. Infection of mice with this recombinant adenovirus that expresses SP‐E7‐KDEL showed interferon induction and tumour‐protection response, similar to that provided by an adenovirus expressing the E7 antigen fused to CRT. This work demonstrated that just by adding a SP and the KDEL sequence, antigens can be targeted and retained in the ER with a consequent enhancement of immune response and tumour protection. These results will have significant clinical applications.