title: The aminopeptidase ERAAP shapes the peptide repertoire displayed by major histocompatibility complex class I molecules.
abstract: Major histocompatibility complex (MHC) class I molecules present thousands of peptides to allow CD8(+) T cells to detect abnormal intracellular proteins. The antigen-processing pathway for generating peptides begins in the cytoplasm, and the MHC molecules are loaded in the endoplasmic reticulum. However, the nature of peptide pool in the endoplasmic reticulum and the proteolytic events that occur in this compartment are unclear. We addressed these issues by generating mice lacking the endoplasmic reticulum aminopeptidase associated with antigen processing (ERAAP). We found that loss of ERAAP disrupted the generation of naturally processed peptides in the endoplasmic reticulum, decreased the stability of peptide-MHC class I complexes and diminished CD8(+) T cell responses. Thus, trimming of antigenic peptides by ERAAP in the endoplasmic reticulum is essential for the generation of the normal repertoire of processed peptides.
authors.affiliation: Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200, USA.
authors.forename: Gianna Elena
authors.initials: GE
authors.lastname: Hammer
authors.forename: Federico
authors.initials: F
authors.lastname: Gonzalez
authors.forename: Marine
authors.initials: M
authors.lastname: Champsaur
authors.forename: Dragana
authors.initials: D
authors.lastname: Cado
authors.forename: Nilabh
authors.initials: N
authors.lastname: Shastri
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015139:Blotting, Southern; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002851:Chromatography, High Pressure Liquid; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007931:Leucyl Aminopeptidase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D014162:Transfection
chemical_list: D015395:Histocompatibility Antigens Class I; D010455:Peptides; D007931:Leucyl Aminopeptidase; C456799:puromycin-insensitive leucyl-specific aminopeptidase