title: The TAP translocation machinery in adaptive immunity and viral escape mechanisms.
abstract: The adaptive immune system plays an essential role in protecting vertebrates against a broad range of pathogens and cancer. The MHC class I-dependent pathway of antigen presentation represents a sophisticated cellular machinery to recognize and eliminate infected or malignantly transformed cells, taking advantage of the proteasomal turnover of the cell's proteome. TAP (transporter associated with antigen processing) 1/2 (ABCB2/3, where ABC is ATP-binding cassette) is the principal component in the recognition, translocation, chaperoning, editing and final loading of antigenic peptides on to MHC I complexes in the ER (endoplasmic reticulum) lumen. These different tasks are co-ordinated within a dynamic macromolecular peptide-loading complex consisting of TAP1/2 and various auxiliary factors, such as the adapter protein tapasin, the oxidoreductase ERp57, the lectin chaperone calreticulin, and the final peptide acceptor the MHC I heavy chain associated with β2-microglobulin. In this chapter, we summarize the structural organization and molecular mechanism of the antigen-translocation machinery as well as various modes of regulation by viral factors and in genetic diseases and tumour development.
authors.affiliation: Institute of Biochemistry, Goethe University Frankfurt, Max-von-Laue Strasse 9, D-60438 Frankfurt/Main, Germany.
authors.forename: Rupert
authors.initials: R
authors.lastname: Abele
authors.forename: Robert
authors.initials: R
authors.lastname: Tampé
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D056704:Adaptive Immunity; D000255:Adenosine Triphosphate / Q000502:physiology; D030342:Genetic Diseases, Inborn / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000276:immunology / Q000473:pathology; D011487:Protein Conformation; D021381:Protein Transport; D019139:Tumor Escape; D018406:Virus Physiological Phenomena
chemical_list: D018528:ATP-Binding Cassette Transporters; C477327:transporter associated with antigen processing (TAP); D000255:Adenosine Triphosphate