Abstracts (complete list) - Wissenschaft Online

Sascha Barabas, Tanja Bauer, Regina Gary, Petra Lindner, Juha Lindner, Wolfgang
Jilg, Hans Wolf, Ludwig Deml
Urea-mediated cross-presentation of soluble Epstein-Barr
Virus BZLF1
Soluble extracellular polypeptides are almost exclusively delivered to the exogenous
MHC class II presentation pathway of antigen-presenting cells (APC), thus diminishing
their capacity to stimulate CD8+ cytotoxic T lymphocytes (CTL). Here, we describe the
urea-mediated translocation of soluble Epstein-Barr virus (EBV) immediate early protein
BZLF1 to the endogenous cytosolic pathway of MHC I-dependent polypeptide
presentation.
APC pulsed with urea-treated BZLF1 (uBZLF1) efficiently reactivate BZLF1-specific CTL
and T helper cells from HLA-matched EBV-seropositive donors. uBZLF1 shows strong
attachment to the cell membrane before uptake by clathrin-mediated endocytosis and
degradation at the proteasome for cross-presentation. Dendritic cells, monocytes but
also B cells are able to mediate MHC I-restricted epitope presentation from uBZLF1. This
strategy considerably promotes reactivation and propagation of protein-specific CTL.
The procedure described here has potential for use in evolving improved strategies for
protein-specific monitoring and immunotherapy of viral infections.