Abstracts (complete list) - Wissenschaft Online

Andreas Goldwich, Sabine Hahn, Sandra Schreiber, Ralf Wagner, Manfred Lutz,
Eckhardt Kämpgen, Ulrich Schubert
Targeting HIV-1 Gag into the DRiP-Pathway results in
enhanced CD8 T cell activation
The main source of peptides presented by the MHC-I pathway are proteins degraded via
the ubiquitin proteasome pathway. Different protein substrate pools can be
distinguished: first, short-lived defective ribosomal products (DRiPs) which are
degraded in concert with or shortly after their synthesis, and second, functional proteins
which are entering the standard protein live cycle.
To analyze the contribution of these substrates to the generation of MHC- I-presented
peptides, we established murine cell lines which express HIV-1 Gag variants harboring
degron signals and the murine OVA-derived MHC-I model epitope SIINFEKL (SL).
Although an HIV-1 Gag variant harboring an N-end degron (UbRGag) displayed wt half
life, its inherent DRiP-rate was increased, resulting in enhanced MHC-I Ag presentation.
Additionally, this increased presentation causes a better T cell stimulation of SL-specific
B3Z hybridoma cells in vitro and adoptively transferred OT-1 T cells in vivo.
Futhermore, enhanced numbers of SL-specific T cells in vivo were detected by IFN-γ
ELISPOT after vaccination of naïve C57Bl6 mice in the case of the UbRGag variant.
These results point out the importance of the DRiP-pathway in adaptive immunity and
may be relevant for further vaccination studies against tumors or intracellular
pathogens.