Professional APCs (pAPC) can process and present on their own MHC class I molecules Ags acquired from Ag donor cells (ADC). This phenomenon of cross-presentation is essential in the induction of CD8(+) T cell responses to viruses that do not infect pAPC and possibly contributes to the induction of CD8(+) responses to many other viruses. However, little is known about the mechanisms underlying this process. In this study, we show that dendritic cells and macrophages cross-present a model Ag supplied by vaccinia virus-infected ADC via the cytosolic route. Strikingly, we also found that cross-presentation of Ags provided by vaccinia-infected cells occurs within a couple of hours of pAPC/ADC interaction, that the duration of cross-presentation lasts for only 16 h, and that cross-presentation can occur at early times of infection when the ADC are still alive.

Priming of CD8+ T cells requires presentation of short peptides bound to MHC class I molecules of professional APCs. Cross-presentation is a mechanism whereby professional APC present on their own MHC class I molecules peptides derived from degradation of Ags synthesized by other Ag “donor cells.” The mechanism of cross-presentation is poorly understood, and the nature of the transferred Ag is unknown. In this report, we demonstrate that the bulk of a cross-presented Ag transferred from donor cells recently infected with vaccinia virus are proteasomal products that are susceptible to peptidases within the donor cell cytosol and not full-length proteins or mature epitopes either free or bound to chaperones.

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