Antigen derived from engulfed apoptotic cells can be cross-presented by dendritic cells (DCs) for the generation of major histocompatibility class I/peptide complexes. While the early events of recognition and internalization of the dying cell have been characterized, the antigen-processing pathway or pathways remain unknown. We established a mouse model assaying for the activation of polyclonal T cells reactive to antigen derived from apoptotic cells, and demonstrated two distinct pathways for the trafficking of exogenous epitopes. In the first, exogenous antigen is dependent on the DC's expression of a functional transporter associated with antigen processing (TAP). Surprisingly, we found evidence that a second pathway exists in which transfer of processed antigen from the dying cell allows formation of major histocompatibility class I/peptide complexes in TAP-deficient DCs. In vivo data suggest that in situations of stress (e.g., viral infection), this latter pathway may be more efficient, illustrating that dying cells may preselect immunologically important antigenic determinants.