Project Members

Valentina Herbring
PhD Student
phone: +49-(0)-69-798-29505

Viral Immune Evasion – Game of Hide-and-Seek

Viruses have evolved sophisticated strategies to evade the immune response, which results in lifelong persistence in the host. So far, five different viral factors–four encoded by Herpesviridae, one by Orthopoxviridae–have been identified that are known to inhibit antigen translocation by the TAP complex. Mechanistically, viral sabotage of TAP includes the inhibition of peptide binding to TAP, the prevention of ATP binding and hydrolysis, and the degradation of TAP via the ER associated degradation (ERAD) pathway. These viral proteins have turned out to be powerful tools to elucidate the structure, mechanism, physiological function of the TAP and peptide-loading complex in different antigen processing pathways.


We aim at identifying new viral factors, which block the antigen processing. Detailed knowledge about inhibitory assemblies and networks of the antigen processing machinery will stimulate the development of potent immune suppressors and antiviral drugs. This may include novel vaccination strategies to restore the immune response against infected cells.

Publications:

Mayerhofer PU, Tampé R.J
Antigen Translocation Machineries in Adaptive Immunity and Viral Immune Evasion.
Mol Biol. 2014 Sep 12. pii: S0022-2836(14)00493-8.    PDF

Priyanka Nair-Gupta, Alessia Baccarini, Navpreet Tung, Fabian Seyffer, Oliver Florey, Yunjie Huang, Meenakshi Banerjee, Michael Overholtzer, Paul A. Roche, Robert Tampé, Brian D. Brown, Derk Amsen, Sidney W. Whiteheart, J. Magarian Blander
TLR Signals Induce Phagosomal MHC-I Delivery from the Endosomal Recycling Compartment to Allow Cross-Presentation
Cell. 2014 July 31;158(6):506–21.   PDF

Wycisk AI, Lin J, Loch S, Hobohm K, Funke J, Wieneke R, Koch J, Skach WR, Mayerhofer PU, Tampé R. (2011) Epstein-Barr viral BNLF2a hijacks the tail-anchored protein insertion machinery to block antigen processing by the TAP complex. J Biol Chem. 2011 286: 41402–41412.   PDF

Loch, S., Klauschies, F., Schölz, C., Verweij, M.C., Wiertz, E.J.H.J., Koch, J. & 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.     PDF