2026-06-15T16:14:53Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/96952025-05-30T16:41:28Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Guil, Sara
author
Rodríguez-Castro, Marta
author
Aguilar, Francisco
author
Villasevil, Eugenia M
author
Antón, Luis C
author
Val, Margarita del
funder
Ministerio de Educación y Ciencia (España)
funder
Instituto de Salud Carlos III
funder
Fundación Ramón Areces
funder
Comunidad de Madrid (España)
2020-04-23T06:59:33Z
2020-04-23T06:59:33Z
2006-12-29
J Biol Chem. 2006 Dec 29;281(52):39925-34. Epub 2006 Nov 6.
10.1074/jbc.M608522200
0021-9258
The Journal of biological chemistry
17088258
http://hdl.handle.net/20.500.12105/9695
CD8(+) T lymphocytes recognize infected cells that display virus-derived antigenic peptides complexed with major histocompatibility complex class I molecules. Peptides are mainly byproducts of cellular protein turnover by cytosolic proteasomes. Cytosolic tripeptidyl-peptidase II (TPPII) also participates in protein degradation. Several peptidic epitopes unexpectedly do not require proteasomes, but it is unclear which proteases generate them. We studied antigen processing of influenza virus nucleoprotein epitope NP(147-155), an archetype epitope that is even destroyed by a proteasome-mediated mechanism. TPPII, with the assistance of endoplasmic reticulum trimming metallo-aminopeptidases, probably ERAAP (endoplasmic reticulum aminopeptidase associated with antigen processing), was crucial for nucleoprotein epitope generation both in the presence of functional proteasomes and when blocked by lactacystin, as shown with specific chemical inhibitors and gene silencing. Different protein contexts and subcellular targeting all allowed epitope processing by TPPII as well as trimming. The results show the plasticity of the cell's assortment of proteases for providing ligands for recognition by antiviral CD8(+) T cells. Our observations identify for the first time a set of proteases competent for antigen processing of an epitope that is susceptible to destruction by proteasomes.
eng
Need for tripeptidyl-peptidase II in major histocompatibility complex class I viral antigen processing when proteasomes are detrimental
research article
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NeedForTripeptidylPeptidase_2003.pdf
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NeedForTripeptidylPeptidase_2003.pdf.txt