Control of CD8+ T cells through interference of cytomegalovirus with the peptide loading complex (PLC)

MHC I antigen presentation to CD8+ T-cells is a major mechanism of immune defense against virally infected cells. Human cytomegalovirus (HCMV) encodes for several post-translational strategies which have been extensively studied recently. Within this project the peptide loading complex (PLC) in naturally HCMV-infected cells was analyzed and the composition of the PLC throughout HCMV replication was monitored. Metabolic labeling experiments have revealed not only the absence of MHC I incorporation into the PLC during early time points of infection, but also lack of tapasin starting at early but being most pronounced at late times of infection. Furthermore, also reduction of TAP1 and TAP2 transcription was observed contrasting the elevated levels of MHC I transcripts. Within the 2nd funding period firstly the molecular basis of tapasin dissociation from MHC class I during HCMV infection will be analysed and secondly PLC regulating factors will be identified which will allow the analysis of MHC I presented antigens during HCMV infection after repairing PLC assembly and function. This strategy of research will be important not only for the evaluation of the escape of CD8+ T cell recognition by HCMV but also for HCMV vaccine design.

Dr. Anne Halenius, Prof. Dr. Hartmut Hengel
Institute of Virology,  Heinrich-Heine-University of Düsseldorf

TP8 in period 2007-2009

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