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In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules

Endoplasmic reticulum (ER)-associated aminopeptidase (ERAP)1 has been implicated in the final proteolytic processing of peptides presented by major histocompatibility complex (MHC) class I molecules. To evaluate the in vivo role of ERAP1, we have generated ERAP1-deficient mice. Cell surface expressi...

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Autores principales: Yan, Jingbo, Parekh, Vrajesh V., Mendez-Fernandez, Yanice, Olivares-Villagómez, Danyvid, Dragovic, Srdjan, Hill, Timothy, Roopenian, Derry C., Joyce, Sebastian, Van Kaer, Luc
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118255/
https://www.ncbi.nlm.nih.gov/pubmed/16505142
http://dx.doi.org/10.1084/jem.20052271
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author Yan, Jingbo
Parekh, Vrajesh V.
Mendez-Fernandez, Yanice
Olivares-Villagómez, Danyvid
Dragovic, Srdjan
Hill, Timothy
Roopenian, Derry C.
Joyce, Sebastian
Van Kaer, Luc
author_facet Yan, Jingbo
Parekh, Vrajesh V.
Mendez-Fernandez, Yanice
Olivares-Villagómez, Danyvid
Dragovic, Srdjan
Hill, Timothy
Roopenian, Derry C.
Joyce, Sebastian
Van Kaer, Luc
author_sort Yan, Jingbo
collection PubMed
description Endoplasmic reticulum (ER)-associated aminopeptidase (ERAP)1 has been implicated in the final proteolytic processing of peptides presented by major histocompatibility complex (MHC) class I molecules. To evaluate the in vivo role of ERAP1, we have generated ERAP1-deficient mice. Cell surface expression of the class Ia molecules H-2K(b) and H-2D(b) and of the class Ib molecule Qa-2 was significantly reduced in these animals. Although cells from mutant animals exhibited reduced capacity to present several self- and foreign antigens to K(b)-, D(b)-, or Qa-1(b)–restricted CD8(+) cytotoxic T cells, presentation of some antigens was unaffected or significantly enhanced. Consistent with these findings, mice generated defective CD8(+) T cell responses against class I–presented antigens. These findings reveal an important in vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules.
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spelling pubmed-21182552007-12-13 In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules Yan, Jingbo Parekh, Vrajesh V. Mendez-Fernandez, Yanice Olivares-Villagómez, Danyvid Dragovic, Srdjan Hill, Timothy Roopenian, Derry C. Joyce, Sebastian Van Kaer, Luc J Exp Med Articles Endoplasmic reticulum (ER)-associated aminopeptidase (ERAP)1 has been implicated in the final proteolytic processing of peptides presented by major histocompatibility complex (MHC) class I molecules. To evaluate the in vivo role of ERAP1, we have generated ERAP1-deficient mice. Cell surface expression of the class Ia molecules H-2K(b) and H-2D(b) and of the class Ib molecule Qa-2 was significantly reduced in these animals. Although cells from mutant animals exhibited reduced capacity to present several self- and foreign antigens to K(b)-, D(b)-, or Qa-1(b)–restricted CD8(+) cytotoxic T cells, presentation of some antigens was unaffected or significantly enhanced. Consistent with these findings, mice generated defective CD8(+) T cell responses against class I–presented antigens. These findings reveal an important in vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules. The Rockefeller University Press 2006-03-20 /pmc/articles/PMC2118255/ /pubmed/16505142 http://dx.doi.org/10.1084/jem.20052271 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Yan, Jingbo
Parekh, Vrajesh V.
Mendez-Fernandez, Yanice
Olivares-Villagómez, Danyvid
Dragovic, Srdjan
Hill, Timothy
Roopenian, Derry C.
Joyce, Sebastian
Van Kaer, Luc
In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules
title In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules
title_full In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules
title_fullStr In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules
title_full_unstemmed In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules
title_short In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules
title_sort in vivo role of er-associated peptidase activity in tailoring peptides for presentation by mhc class ia and class ib molecules
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118255/
https://www.ncbi.nlm.nih.gov/pubmed/16505142
http://dx.doi.org/10.1084/jem.20052271
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