AUTHOR=Kim Sun Jin , Sin Jeong-Im , Kim Min Ja 

TITLE=CD8+ T Cells Directed Against a Peptide Epitope Derived From Peptidoglycan-Associated Lipoprotein of Legionella pneumophila Confer Disease Protection

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.604413

DOI=10.3389/fimmu.2020.604413

ISSN=1664-3224

ABSTRACT=<p><italic>Legionella pneumophila</italic>, an intracellular bacterium, may cause life-threatening pneumonia in immunocompromised individuals. Mononuclear cells and antibodies have been reported to be associated with the host defense response against <italic>L. pneumophila.</italic> This study is to determine whether <italic>Legionella</italic> peptidoglycan-associated lipoprotein (PAL)-specific CD8<sup>+</sup> T cells are directly associated with protection against <italic>L. pneumophila</italic>, with a focus on potential epitopes. Synthetic peptides derived from PAL of <italic>L. pneumophila</italic> were obtained and tested through in <italic>vitro</italic> and <italic>in vivo</italic> cytotoxic T lymphocyte (CTL) assays for immunogenicity. PAL DNA vaccines or a peptide epitope with or without CpG-oligodeoxynucleotides (ODN) was evaluated for protection against <italic>L. pneumophila</italic> infection in animal models. When mice were immunized with DNA vaccines expressing the PAL of <italic>L. pneumophila</italic>, they were significantly protected against a lethal challenge with <italic>L. pneumophila</italic> through induction of antigen-specific CD8<sup>+</sup> CTLs. Of the 13 PAL peptides tested, PAL<sub>92-100</sub> (EYLKTHPGA) was the most immunogenic and induced the strongest CTL responses. When mice were immunized with the PAL<sub>92-100</sub> peptide plus CpG-ODN, they were protected against the lethal challenge, while control mice died within 3–6 days after the challenge. Consistent with lung tissue histological data, bacterial counts in the lungs of immunized mice were significantly lower than those in control mice. Also, the amino acid sequence of PAL<sub>92-100</sub> peptides is conserved among various <italic>Legionella</italic> species. To our knowledge, this study is the first to demonstrate that PAL<sub>92-100</sub>-specific CD8<sup>+</sup> T cells play a central role in the host defense response against <italic>L. pneumophila</italic>.</p>