Tapasin-the keystone of the loading complex optimizing peptide binding by MHC class I molecules in the endoplasmic reticulum.
MHC class I molecules are loaded with peptides that mostly originate from the degradation of cytosolic protein antigens and that are translocated across the endoplasmic reticulum (ER) membrane by the transporter associated with antigen processing (TAP). The ER-resident molecule tapasin (Tpn) is uniquely dedicated to tether class I molecules jointly with the chaperone calreticulin (Crt) and the oxidoreductase ERp57 to TAP. As learned from the study of a Tpn-deficient cell line and from mice harboring a disrupted Tpn gene, the transient association of class I molecules with Tpn and TAP is critically important for the stabilization of class I molecules and the optimization of the peptide cargo presented to cytotoxic T cells. The different functions of molecular domains of Tpn and the highly coordinated formation of the TAP-associated peptide loading complex will also be discussed in this review.
Department of Molecular Immunology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. f.momburg@dkfz.de
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D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation; D017920:Antiporters / Q000235:genetics / Q000502:physiology*; D037282:Calreticulin / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005805:Genes, MHC Class I; D006360:Heat-Shock Proteins / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000502:physiology*; D007535:Isomerases / Q000378:metabolism; D026901:Membrane Transport Proteins; D011110:Polymorphism, Genetic; D019704:Protein Disulfide-Isomerases; D013045:Species Specificity; D001613:beta 2-Microglobulin / Q000502:physiology
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D017920:Antiporters; D037282:Calreticulin; D006360:Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; C073119:TAP1 protein, human; D001613:beta 2-Microglobulin; C107762:tapasin; C071692:TAP2 protein, human; D007535:Isomerases; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human