Targeting and retention of HPV16 E7 to the endoplasmic reticulum enhances immune tumour protection

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 organ...

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Autores principales: Loera Arias, María de Jesús, Martínez Pérez, Alejandra Guadalupe, Barrera Hernández, A., Ibarra Obregón, E. R., González Saldívar, Gerardo, Martínez Ortega, J. I., Rosas Taraco, Adrián Geovanni, Villanueva Olivo, Arnulfo, Esparza González, Sandra Cecilia, Villatoro Hernández, Julio, Saucedo Cárdenas, Odila, Montes de Oca Luna, Roberto
Formato: Artículo
Lenguaje:inglés
Publicado: 2009
Acceso en línea:http://eprints.uanl.mx/15086/1/758.pdf
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author Loera Arias, María de Jesús
Martínez Pérez, Alejandra Guadalupe
Barrera Hernández, A.
Ibarra Obregón, E. R.
González Saldívar, Gerardo
Martínez Ortega, J. I.
Rosas Taraco, Adrián Geovanni
Villanueva Olivo, Arnulfo
Esparza González, Sandra Cecilia
Villatoro Hernández, Julio
Saucedo Cárdenas, Odila
Montes de Oca Luna, Roberto
author_facet Loera Arias, María de Jesús
Martínez Pérez, Alejandra Guadalupe
Barrera Hernández, A.
Ibarra Obregón, E. R.
González Saldívar, Gerardo
Martínez Ortega, J. I.
Rosas Taraco, Adrián Geovanni
Villanueva Olivo, Arnulfo
Esparza González, Sandra Cecilia
Villatoro Hernández, Julio
Saucedo Cárdenas, Odila
Montes de Oca Luna, Roberto
author_sort Loera Arias, María de Jesús
collection Repositorio Institucional
description 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.
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spelling eprints-150862024-03-05T16:14:59Z http://eprints.uanl.mx/15086/ Targeting and retention of HPV16 E7 to the endoplasmic reticulum enhances immune tumour protection Loera Arias, María de Jesús Martínez Pérez, Alejandra Guadalupe Barrera Hernández, A. Ibarra Obregón, E. R. González Saldívar, Gerardo Martínez Ortega, J. I. Rosas Taraco, Adrián Geovanni Villanueva Olivo, Arnulfo Esparza González, Sandra Cecilia Villatoro Hernández, Julio Saucedo Cárdenas, Odila Montes de Oca Luna, Roberto 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. 2009 Article PeerReviewed text en cc_by_nc_nd http://eprints.uanl.mx/15086/1/758.pdf http://eprints.uanl.mx/15086/1.haspreviewThumbnailVersion/758.pdf Loera Arias, María de Jesús y Martínez Pérez, Alejandra Guadalupe y Barrera Hernández, A. y Ibarra Obregón, E. R. y González Saldívar, Gerardo y Martínez Ortega, J. I. y Rosas Taraco, Adrián Geovanni y Villanueva Olivo, Arnulfo y Esparza González, Sandra Cecilia y Villatoro Hernández, Julio y Saucedo Cárdenas, Odila y Montes de Oca Luna, Roberto (2009) Targeting and retention of HPV16 E7 to the endoplasmic reticulum enhances immune tumour protection. Journal of Cellular and Molecular Medicine, 14 (4). pp. 890-894. ISSN 15821838 http://doi.org/10.1111/j.1582-4934.2009.00934.x doi:10.1111/j.1582-4934.2009.00934.x
spellingShingle Loera Arias, María de Jesús
Martínez Pérez, Alejandra Guadalupe
Barrera Hernández, A.
Ibarra Obregón, E. R.
González Saldívar, Gerardo
Martínez Ortega, J. I.
Rosas Taraco, Adrián Geovanni
Villanueva Olivo, Arnulfo
Esparza González, Sandra Cecilia
Villatoro Hernández, Julio
Saucedo Cárdenas, Odila
Montes de Oca Luna, Roberto
Targeting and retention of HPV16 E7 to the endoplasmic reticulum enhances immune tumour protection
thumbnail https://rediab.uanl.mx/themes/sandal5/images/online.png
title Targeting and retention of HPV16 E7 to the endoplasmic reticulum enhances immune tumour protection
title_full Targeting and retention of HPV16 E7 to the endoplasmic reticulum enhances immune tumour protection
title_fullStr Targeting and retention of HPV16 E7 to the endoplasmic reticulum enhances immune tumour protection
title_full_unstemmed Targeting and retention of HPV16 E7 to the endoplasmic reticulum enhances immune tumour protection
title_short Targeting and retention of HPV16 E7 to the endoplasmic reticulum enhances immune tumour protection
title_sort targeting and retention of hpv16 e7 to the endoplasmic reticulum enhances immune tumour protection
url http://eprints.uanl.mx/15086/1/758.pdf
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