title: ERAAP synergizes with MHC class I molecules to make the final cut in the antigenic peptide precursors in the endoplasmic reticulum.
abstract: The major histocompatibility complex class I molecules display peptides (pMHC I) on the cell surface for immune surveillance by CD8(+) T cells. These peptides are generated by proteolysis of intracellular polypeptides by the proteasome in the cytoplasm and then in the endoplasmic reticulum (ER) by the ER aminopeptidase associated with antigen processing (ERAAP). To define the unknown mechanism of ERAAP function in vivo, we analyzed naturally processed peptides in cells with or without appropriate MHC I and ERAAP. In the absence of MHC I, ERAAP degraded the antigenic precursors in the ER. However, MHC I molecules could bind proteolytic intermediates and were essential for generation of the final peptide by ERAAP. Thus, ERAAP synergizes with MHC I to generate the final pMHC I repertoire.
authors.affiliation: Division of Immunology, Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kanaseki
authors.forename: Nicolas
authors.initials: N
authors.lastname: Blanchard
authors.forename: Gianna Elena
authors.initials: GE
authors.lastname: Hammer
authors.forename: Federico
authors.initials: F
authors.lastname: Gonzalez
authors.forename: Nilabh
authors.initials: N
authors.lastname: Shastri
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D000941:Antigens / Q000737:chemistry / Q000276:immunology*; D002851:Chromatography, High Pressure Liquid; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism*; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007931:Leucyl Aminopeptidase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D016133:Polymerase Chain Reaction; D014162:Transfection
chemical_list: D000941:Antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D007931:Leucyl Aminopeptidase; C456799:puromycin-insensitive leucyl-specific aminopeptidase