An evaluation of the efficiency of lymphocytic choriomeningitis virus - nucleoprotein cross priming in vivo

Abstract

During viral infections, CD8+ T cells only respond to a select few epitopes derived from the respective foreign pathogen. These epitopes can be organized into a hierarchy, based on their ability to induce T cell priming. Such phenomenon is known as immunodominance. Cytotoxic T cells can be primed through the direct pathway, or the cross-priming pathway. The latter involves exogenously derived viral epitope presentation by uninfected professional antigen presenting cells. It has been previously reported that Lymphocytic Choriomeningitis nucleoprotein expressed in HEK cells (HEK-NP) could be cross presented to CD8+ T cells. In these studies we have used this same HEK-NP model to study the effects of LCMV-NP cross priming on the LCMV immunodominance hierarchy following viral challenge. Our results provide strong evidence that cross priming is an efficient route with which to induce cell-mediated immunity. We also highlight a regulatory role for cross priming in immunodominance by showing that a single dose of HEK-NP can completely shift the immunodominance hierarchy of a typical LCMV infection. Furthermore, we see that the induction of LCMV-NP cross priming boosts anti-viral immunity to subsequent LCMV infections. This work provides strong support for the physiological role that cross priming plays in normal cell-mediated immune responses. It may also provide relevant information to the realm of immunotherapy.