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-2Kb and H-2Db 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 Kb-, Db-, or Qa-1b–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.
Skip Nav Destination
Article navigation
20 March 2006
Article|
February 27 2006
In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules
Jingbo Yan,
Jingbo Yan
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Search for other works by this author on:
Vrajesh V. Parekh,
Vrajesh V. Parekh
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Search for other works by this author on:
Yanice Mendez-Fernandez,
Yanice Mendez-Fernandez
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Search for other works by this author on:
Danyvid Olivares-Villagómez,
Danyvid Olivares-Villagómez
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Search for other works by this author on:
Srdjan Dragovic,
Srdjan Dragovic
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Search for other works by this author on:
Timothy Hill,
Timothy Hill
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Search for other works by this author on:
Derry C. Roopenian,
Derry C. Roopenian
2The Jackson Laboratory, Bar Harbor, ME 04609
Search for other works by this author on:
Sebastian Joyce,
Sebastian Joyce
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Search for other works by this author on:
Luc Van Kaer
Luc Van Kaer
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Search for other works by this author on:
Jingbo Yan
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Vrajesh V. Parekh
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Yanice Mendez-Fernandez
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Danyvid Olivares-Villagómez
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Srdjan Dragovic
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Timothy Hill
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Derry C. Roopenian
2The Jackson Laboratory, Bar Harbor, ME 04609
Sebastian Joyce
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
Luc Van Kaer
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
CORRESPONDENCE Luc Van Kaer: [email protected]
Abbreviations used: Endo H, endoglycosidase H; ERAP, ER-associated aminopeptidase; ES, embryonic stem; LCMV, lymphocytic choriomeningitis virus; Qdm, Qa-1 determinant modifier; TAP, transporter of antigen presentation.
J. Yan and V.V. Parekh contributed equally to this work.
Received:
November 14 2005
Accepted:
February 01 2006
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2006
J Exp Med (2006) 203 (3): 647–659.
Article history
Received:
November 14 2005
Accepted:
February 01 2006
Citation
Jingbo Yan, Vrajesh V. Parekh, Yanice Mendez-Fernandez, Danyvid Olivares-Villagómez, Srdjan Dragovic, Timothy Hill, Derry C. Roopenian, Sebastian Joyce, Luc Van Kaer; In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules . J Exp Med 20 March 2006; 203 (3): 647–659. doi: https://doi.org/10.1084/jem.20052271
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement