The Use of Bone Marrow-Chimeric Mice in Determining the MHC Restriction of Epitope-Specific Cytotoxic T Lymphocytes

Abstract

Plasmid DNA immunization has emerged as a promising vaccine strategy against infectious agents, as well as a potential intervention for the treatment of cancer, autoimmunity, and allergy (1). Until recently, however, the cellular events by which injected plasmid DNA elicits potent antibody and cytotoxic T-lymphocyte (CTL) responses were largely unknown. Upon intramuscular (i.m.) injection of naked DNA, predominant expression of transfected DNA occurs in the myofibers (2), but no direct transfection of antigen presenting cells (APC) has been reported. There are essentially three different mechanisms by which CTLs can be primed by the injected DNA (3). The first possibility is that the transfected muscle cells directly activate CTLs by presenting the antigenic peptide on their MHC class I molecules. Alternatively, the priming of CTLs may be mediated by professional APC taking up antigen released from muscle cells. Finally, CTL priming may involve direct transfection of APC occurring, albeit at low level, and that the CTLs are activated by the transfected APC.