MHC class I antigen presentation in human cytomegalovirus infection
The research interests of our group focus on MHC class I antigen presentation in cells infected by human cytomegalovirus (HCMV). HCMV belongs to the β-subgroup of herpesviruses and is one of the largest viruses known to infect humans. HCMV possesses an imposing coding capacity with several hundreds of viral proteins being expressed in infected cells. A large fraction of these proteins is dedicated to counteract host immune defense mechanisms and enables the virus to persist in the host for a life-time. In immunocompromised hosts, infection might have pathological and even fatal consequences, whereas a healthy immune system is able to control the infection.
Analysis of MHC class I antigen presentation in HCMV infection (B: Halenius et al., Journal of Virology 85(7):3473-85).
HCMV encodes for several glycoproteins that reduce cell surface expression of MHC class I molecules and prohibit CD8+ T cell recognition of infected cells. Since CD8+ T-cells are nonetheless able to restrict the infection, the inhibition of MHC class I antigen presentation by HCMV is not complete. So far, a seemingly limited number of HCMV-specific CD8+ T cells have been identified in CMV-positive persons, but not much is known about which potential antigens escape HCMV control in infected cells and which do not and how this is regulated. We investigate the inhibitory mechanisms of HCMV on MHC class I antigen presentation and the contribution of these mechanisms to form the HCMV specific MHC class I ligandome.
Collaboration partners:
- Frank Momburg (DKFZ, Heidelberg)
- Stefan Stevanović (University of Tübingen, Tübingen)
- Richard Berry (Monash University, Clayton, Australia)
- Stipan Jonjić (University of Rijeka, Rijeka, Croatia)
- Sebastian Springer (Jacobs University, Bremen)
Selected References:
- Beutler N, Hauka S, Niepel A, Kowalewski DJ, Uhlmann J, Ghanem E, Erkelenz S, Wiek C, Hanenberg H, Schaal H, Stevanovic S, Springer S, Momburg F, Hengel H, Halenius A. 2013. A natural tapasin isoform lacking exon 3 modifies peptide loading complex function. European Journal of Immunology 43(6):1459-69.
- Halenius A., Hauka S., Dölken L., Stindt J., Reinhard H., Wiek C., Hanenberg H., Koszinowski U.H., Momburg F., Hengel H. 2011. Human Cytomegalovirus Disrupts the MHC Class I Peptide Loading Complex (PLC) and Inhibits Tapasin Gene Transcription. Journal of Virology 85(7):3473-85.
- Verweij M.C., Ressing M.E., Knetsch W., Quinten E., Halenius A., van Beld N., Hengel H., Drijfhoute J.W., van Hall T.,Wiertz E.J. 2010. Herpesvirus-encoded immune evasion molecules cross species barriers to inhibit mouse MHC class I-restricted antigen presentation. Molecular Immunology 48(6-7):835-45.
- Halenius A., Momburg F., Reinhard H., Bauer D., Lobigs M., Hengel H. 2006. Physical and functional interactions of the cytomegalovirus US6 glycoprotein with the transporter associated with antigen processing, Journal of Biological Chemistry 281(9):5383-90.
Institute of Virology
Hermann-Herder-Strasse 11
D-79104 Freiburg
Head
Prof. Dr. med. Hartmut Hengel
hartmut.hengel@uniklinik-freiburg.de
Team Leader
Anne Halenius (Ph.D.)
Phone: +49 761 203 6619
Fax: +49 761 203 6626
