title: MHC class I antigen processing and presenting machinery: organization, function, and defects in tumor cells.
abstract: The surface presentation of peptides by major histocompatibility complex (MHC) class I molecules is critical to all CD8(+) T-cell adaptive immune responses, including those against tumors. The generation of peptides and their loading on MHC class I molecules is a multistep process involving multiple molecular species that constitute the so-called antigen processing and presenting machinery (APM). The majority of class I peptides begin as proteasome degradation products of cytosolic proteins. Once transported into the endoplasmic reticulum by TAP (transporter associated with antigen processing), peptides are not bound randomly by class I molecules but are chosen by length and sequence, with peptidases editing the raw peptide pool. Aberrations in APM genes and proteins have frequently been observed in human tumors and found to correlate with relevant clinical variables, including tumor grade, tumor stage, disease recurrence, and survival. These findings support the idea that APM defects are immune escape mechanisms that disrupt the tumor cells' ability to be recognized and killed by tumor antigen-specific cytotoxic CD8(+) T cells. Detailed knowledge of APM is crucial for the optimization of T cell-based immunotherapy protocols.
authors.affiliation: Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Leone
authors.forename: Eui-Cheol
authors.initials: EC
authors.lastname: Shin
authors.forename: Federico
authors.initials: F
authors.lastname: Perosa
authors.forename: Angelo
authors.initials: A
authors.lastname: Vacca
authors.forename: Franco
authors.initials: F
authors.lastname: Dammacco
authors.forename: Vito
authors.initials: V
authors.lastname: Racanelli
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation; D001693:Biological Transport, Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D018832:Molecular Chaperones / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology*; D010455:Peptides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000276:immunology*
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; D015778:Minor Histocompatibility Antigens; D018832:Molecular Chaperones; D010455:Peptides; C073119:TAP1 protein, human; C071692:TAP2 protein, human; D000626:Aminopeptidases; C464841:ERAP1 protein, human; C503944:ERAP2 protein, human; D046988:Proteasome Endopeptidase Complex