title: In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Yan
authors.forename: Vrajesh V
authors.initials: VV
authors.lastname: Parekh
authors.forename: Yanice
authors.initials: Y
authors.lastname: Mendez-Fernandez
authors.forename: Danyvid
authors.initials: D
authors.lastname: Olivares-Villagómez
authors.forename: Srdjan
authors.initials: S
authors.lastname: Dragovic
authors.forename: Timothy
authors.initials: T
authors.lastname: Hill
authors.forename: Derry C
authors.initials: DC
authors.lastname: Roopenian
authors.forename: Sebastian
authors.initials: S
authors.lastname: Joyce
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
mesh_terms: D000626:Aminopeptidases / Q000172:deficiency / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D010455:Peptides / Q000276:immunology*
chemical_list: D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D015778:Minor Histocompatibility Antigens; D010455:Peptides; C032907:Q surface antigens; D000626:Aminopeptidases; C509944:ERAP1 protein, mouse