Identification of Chlamydia pneumoniae-derived mouse CD8 epitopes.
Chlamydia pneumoniae is a common intracellular human pathogen that has been associated with several severe pathological conditions, including coronary heart disease and atherosclerosis. There is no vaccine against C. pneumoniae infection, but CD8(+) T cells have been shown to be crucial for protection during experimental infection. However, the effector functions and epitope specificity of the protective CD8(+) T cell remain unknown. The aim of this study was to identify C. pneumoniae-derived mouse CD8 epitopes by using a recent epitope prediction method. Of four C. pneumoniae proteins (the major outer membrane protein, outer membrane protein 2, polymorphic outer membrane protein 5, and heat shock protein 60), 53 potential CD8(+) T-cell epitopes were predicted by H-2 class I binding algorithms. Nineteen of the 53 peptides were identified as CD8 epitopes by testing for induction of a cytotoxic response after immunization. To test whether the predicted epitopes are naturally processed and presented by C. pneumoniae-infected cells, we generated a panel of seven peptide-specific cytotoxic T lymphocyte lines that were subsequently tested for recognition of C. pneumoniae-infected target cells. By using this strategy, we were able to identify three C. pneumoniae CD8 epitopes that were, indeed, processed and presented on infected cells. Identification of these natural CD8 epitopes provides tools for characterization of CD8(+) T-cell function in vivo and generation of epitope-specific prevention strategies.
Sarén
Anne
A
Department of Vaccines, National Public Health Institute, Helsinki, Finland. anne.saren@ktl.fi
Pascolo
Steve
S
Stevanovic
Stefan
S
Dumrese
Tilman
T
Puolakkainen
Mirja
M
Sarvas
Matti
M
Rammensee
Hans-Georg
HG
Vuola
Jenni M
JM
D016475:3T3 Cells; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; C101031:major outer membrane protein, Chlamydia pneumoniae