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 different CD8 T cell epitopes of Listeria monocytogenes was monitored. Peptide presentation 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 ELISPOT assay. Remarkably, the peptide presentation pattern of splenocytes and that of macrophages purified from spleens of L. monocytogenes-infected mice were different from those of in vitro infected macrophage-like cell lines. The in vivo Ag presentation pattern of splenocytes also exhibited dynamic 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 highly dynamic process that only can be fully appreciated by the study of cells infected in their physiological environment.
Skoberne
M
M
Institut für Medizinische Mikrobiologie und Hygiene, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany.
Holtappels
R
R
Hof
H
H
Geginat
G
G
D000818:Animals; D017951:Antigen Presentation; D001426:Bacterial Proteins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D001427:Bacterial Toxins; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D006360:Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism; D006460:Hemolysin Proteins; D007275:Injections, Intravenous; D007700:Kinetics; D007941:Leukemia P388; D008089:Listeria monocytogenes / Q000276:immunology*; D018655:Lymphocyte Count; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D009928:Organ Specificity / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D014407:Tumor Cells, Cultured
C078516:60 kDa protein, Listeria monocytogenes; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D018984:Epitopes, T-Lymphocyte; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D010446:Peptide Fragments; C038705:hlyA protein, Listeria monocytogenes