Principal Investigator
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P16 Robert Tampé
Professor and Director
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Institute of Biochemistry
Biocenter
Goethe-University Frankfurt a.M.
Max-von-Laue-Str. 9
60438 Frankfurt am Main, Germany
Phone +49 (0)69 79 82 94 75
Fax +49 (0)69 79 82 94 95
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P16 Viral intrinsic modulators of the macromolecular MHC I peptide-loading complex
The ER-resident transport and MHC class I peptide-loading complex (PLC) is essential for antigen presentation to effector cells of the adaptive immune system, which eliminates infected or malignantly transformed cells. Within this project we will investigate the composition, stoichiometry, structural organization as well as crosstalk of subunits within this macromolecular transport complex.
In addition, we will analyze how viral factors modulate the function of the transport complex leading to viral immune evasion. In particular, we will examine the transport inhibition mechanism of the recently identified viral proteins, which employ subtle strategies to block the peptide translocation and loading onto MHC class I molecules.
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Publications
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Baldauf, C., Schrodt, S., Herget, M., Koch, J. and Tampé, R. (2010) Single residue within the antigen translocation complex TAP controls the epitope repertoire by stabilizing a receptive conformation. Proc Natl Acad Sci USA 107, 9135-9140.
Herget, M., Kreissig, N., Kolbe, C., Schölz, C., Schulze, K., Tampé, R. and Abele, R. (2009) Purification and reconstitution of the antigen transport complex TAP: a prerequisite for determination of peptide stoichiometry, ATP binding and hydrolysis. J Biol Chem 284, 33740-337049.
Oancea, G., O’Mara, M., Bennett, D., Tieleman, D.P., Abele, R. and Tampé, R. (2009) Structural arrangement of the transmission interface in the ABC transporter TAP critical in antigen binding and translocation. Proc Natl Acad Sci USA 106, 5551-5556.
Burgdorf, S., Schölz, C., Kautz, A., Tampé, R. and Kurts, C. (2008) Spatial and mechanistic separation of cross-presentation and endogenous antigen presentation. Nature Immunol 9, 558-566.
Loch, S., Klauschies, F., Schölz, C., Verweij, M.C., Wiertz, E.J.H.J., Koch, J. and Tampé, R. (2008) Signaling of a varicelloviral factor across the ER membrane induces destruction of the peptide-loading complex and immune evasion. J Biol Chem 283, 13428-13436.
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Collaborations
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Glaubitz (P6), Prisner (P7), Abele (P9), Kühlbrandt (P1), Michel (P3), Dötsch/Bernhard (P2), Forrest (P8), Schleiff (P17)