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.
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Review Article| September 07 2011
The TAP translocation machinery in adaptive immunity and viral escape mechanisms
Rupert Abele ;
Robert Tampé 1
*Institute of Biochemistry, Goethe University Frankfurt, Max-von-Laue Strasse 9, D-60438 Frankfurt/Main, Germany
†Center for Membrane Proteomics (CMP), Goethe University Frankfurt, Max-von-Laue Strasse 9, D-60438 Frankfurt/Main, Germany
‡Cluster of Excellence Frankfurt (CEF) – Macromolecular Complexes, Biocenter, Goethe University Frankfurt, Max-von-Laue Strasse 9, D-60438 Frankfurt/Main, Germany
1To whom correspondence should be addressed (firstname.lastname@example.org).
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Essays Biochem (2011) 50: 249–264.
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Frances J. Sharom, Rupert Abele, Robert Tampé; The TAP translocation machinery in adaptive immunity and viral escape mechanisms. Essays Biochem 7 September 2011; 50 249–264. doi: https://doi.org/10.1042/bse0500249
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