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Antigen entry into cytosol enabled by liposomal listeriolysin O.(Brief Article)
2002 AUG 14 - (NewsRx.com & NewsRx.net) -- by Maria G. Essig, MS, ELS, senior medical writer - Encapsulation of a protein antigen along with listeriolysin O in a liposome allowed the antigen access into the cytosol, researchers in the U.S. found.
"Cytotoxic T lymphocytes (CTLs) are primed by peptide antigens that are endogenously processed in the cytosol and presented in the context of major histocompatibility complex I (MHC I) molecules of antigen-presenting cells (APCs)," explained Manas Mandal and Kyung-Dall Lee at the University of Michigan. "Exogenous soluble protein antigens do not gain efficient entry into the cytosol of APCs, and therefore requires a special cytosolic delivery method."
Mandal and Lee investigated the use of listeriolysin O (LLO), a pore-forming protein from Listeria monocytogenes, which allows the bacterium to escape its host vacuole and enter the cytosol.
LLO was encapsulated into a liposome along with ovalbumin (OVA) as a protein antigen surrogate. This delivery system allowed the ovalbumin to penetrate into the cytosol of APCs.
When the investigators inoculated mice with the OVA-LLO-liposome, a higher response of cytotoxic T cells (CTL) specific to OVA was produced in comparison to the response provoked by OVA-liposome or OVA alone. The level of antigen-specific CTL precursors also increased, and a significantly greater release of interferon-gamma (IFN-gamma) ...
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