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Delivery of a viral antigen to the class I processing and presentation pathway by Listeria monocytogenes

G. Ikonomidis,Y. Paterson,Ferdynand J Kos,D. A. Portnoy

Published 1994 in Journal of Experimental Medicine

ABSTRACT

Listeria monocytogenes is a facultative intracellular pathogen that grows in the cytoplasm of infected host cells. We examined the capacity of L. monocytogenes to introduce influenza nucleoprotein (NP) into the class I pathway of antigen presentation both in vitro and in vivo. Recombinant L. monocytogenes secreting a fusion of listeriolysin O and NP (LLO-NP) targeted infected cells for lysis by NP-specific class I- restricted cytotoxic T cells. Antigen presentation occurred in the context of three different class I haplotypes in vitro. A hemolysin- negative L. monocytogenes strain expressing LLO-NP was able to present in a class II-restricted manner. However, it failed to target infected cells for lysis by CD8+ T cells, indicating that hemolysin-dependent bacterial escape from the vacuole is necessary for class I presentation in vitro. Immunization of mice with a recombinant L. monocytogenes strain that stably expressed and secreted LLO-NP induced NP-specific CD8+ cytotoxic T lymphocytes. These studies have implications for the use of L. monocytogenes to deliver potentially any antigen to the class I pathway in vivo.

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