title: Proteolytic enzymes involved in MHC class I antigen processing: A guerrilla army that partners with the proteasome.
abstract: Major histocompatibility complex class I proteins (MHC-I) load short peptides derived from proteolytic cleavage of endogenous proteins in any cell of the body, in a process termed antigen processing and presentation. When the source proteins are altered self or encoded by a pathogen, recognition of peptide/MHC-I complexes at the plasma membrane leads to CD8(+) T-lymphocyte responses that clear infections and probably underlie tumor immune surveillance. On the other hand, presentation of self peptides may cause some types of autoimmunity. The peptides that are presented determine the specificity and efficiency of pathogen clearance or, conversely, of immunopathology. In this review we highlight the growing number of peptidases which, as a by-product of their regular activity, can generate peptide epitopes for immune surveillance. These ∼20 peptidases collectively behave as a guerrilla army partnering with the regular proteasome army in generating a variety of peptides for presentation by MHC-I and thus optimally signaling infection.
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-Universidad Autónoma de Madrid), Madrid, Spain. Electronic address: silvialaz@cbm.csic.es.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lázaro
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-Universidad Autónoma de Madrid), Madrid, Spain. Electronic address: dgamarra@cbm.csic.es.
authors.forename: David
authors.initials: D
authors.lastname: Gamarra
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-Universidad Autónoma de Madrid), Madrid, Spain. Electronic address: mdval@cbm.csic.es.
authors.forename: Margarita
authors.initials: M
authors.lastname: Del Val
mesh_terms: D000626:Aminopeptidases / Q000276:immunology / Q000378:metabolism*; D017951:Antigen Presentation / Q000235:genetics*; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D010450:Endopeptidases / Q000276:immunology / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D020689:Exopeptidases / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D010588:Phagosomes / Q000235:genetics / Q000276:immunology; D046988:Proteasome Endopeptidase Complex / Q000276:immunology / Q000378:metabolism; D059748:Proteolysis; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D010450:Endopeptidases; D020689:Exopeptidases; D000626:Aminopeptidases; D046988:Proteasome Endopeptidase Complex
keywords: Antigen processing; CD8(+) cytotoxic T lymphocyte; Epitope; Major Histocompatibility Complex class I; Peptidase; Protease