Dynamic antigen presentation patterns of Listeria monocytogenes-derived CD8 T cell epitopes in vivo

Little information exists regarding the presentation of antigenic peptides in infected tissues. In this study the in vivo presentation of four differe nt CD8 T cell epitopes of Listeria monocytogenes was monitored. Peptide pre sentation was measured by a new, highly sensitive, ex vivo Ag presentation assay that was based on the testing of freshly isolated cells from infected spleens with peptide-specific CD8 T cell lines in an IFN-gamma -specific E LISPOT assay. Remarkably, the peptide presentation pattern of splenocytes a nd that of macrophages purified from spleens of L. monocytogenes-infected m ice were different from those of in vitro infected macrophage-like cell lin es. The in vivo Ag presentation pattern of splenocytes also exhibited dynam ic changes during the first 48 h of infection. In vivo peptide presentation at later time points postinfection was biased toward immunodominant CD8 T cell epitopes, while at an early time point, 6 h postinfection, subdominant and dominant CD8 T cell epitopes were presented with similar strength. In summary, our studies show that Ag presentation during an infection is a hig hly dynamic process that only can be fully appreciated by the study of cell s infected in their physiological environment.