Published online 27 February 2006 doi:10.1084/jem.20052271
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 3, 647-659
In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules
Jingbo Yan1,
Vrajesh V. Parekh1,
Yanice Mendez-Fernandez1,
Danyvid Olivares-Villagómez1,
Srdjan Dragovic1,
Timothy Hill1,
Derry C. Roopenian2,
Sebastian Joyce1, and
Luc Van Kaer1
1 Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
2 The Jackson Laboratory, Bar Harbor, ME 04609
CORRESPONDENCE Luc Van Kaer: luc.van.kaer{at}vanderbilt.edu
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.
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.
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