Function of the transport complex TAP in cellular immune recognition.
The transporter associated with antigen processing (TAP) is essential for peptide loading onto major histocompatibility complex (MHC) class I molecules by translocating peptides into the endoplasmic reticulum. The MHC-encoded ABC transporter works in concert with the proteasome and MHC class I molecules for the antigen presentation on the cell surface for T cell recognition. TAP forms a heterodimer where each subunit consists of a hydrophilic nucleotide binding domain and a hydrophobic transmembrane domain. The transport mechanism is a multistep process composed of an ATP-independent peptide association step which induces a structural reorganization of the transport complex that may trigger the ATP-driven transport of the peptide into the endoplasmic reticulum lumen. By using combinatorial peptide libraries, the substrate selectivity and the recognition principle of TAP have been elucidated. TAP maximizes the degree of substrate diversity in combination with high substrate affinity. This ABC transporter is also unique as it is closely associated with chaperone-like proteins involved in bonding of the substrate onto MHC molecules. Most interestingly, virus-infected and malignant cells have developed strategies to escape immune surveillance by affecting TAP expression or function.
Abele
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Institut für Physiologische Chemie, Philipps-Universität Marburg, Karl-von-Frisch-Str. 1, 35033, Marburg, Germany.
Tampé
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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 / Q000276:immunology* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000938:Antigen-Presenting Cells; D017920:Antiporters / Q000737:chemistry; D001692:Biological Transport; D002462:Cell Membrane / Q000737:chemistry; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D007425:Intracellular Membranes / Q000737:chemistry; D008285:Major Histocompatibility Complex; D026901:Membrane Transport Proteins; D008958:Models, Molecular; D019151:Peptide Library; D010455:Peptides / Q000378:metabolism; D013379:Substrate Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
C412573:ABCB9 protein, human; 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; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D019151:Peptide Library; D010455:Peptides; C073119:TAP1 protein, human; C107762:tapasin; C071692:TAP2 protein, human; D000255:Adenosine Triphosphate