Role of listeriolysin-O (LLO) in the T lymphocyte response to infection with Listeria monocytogenes. Identification of T cell epitopes of LLO.

摘要: Using a murine model, we investigated the role of bacterial exotoxin listeriolysin O (LLO) in cellular immunity to Listeria monocytogenes. A correlation between LLO production by infecting bacteria and generation protective virulent LLO-producing was noted. isogeneic hemolysin (Hly+ or Hly-) strains L. monocytogenes, demonstrated that is required elicit T cells reactive both bacteria-associated Ag secreted molecule as measured IL-2 vitro. Distinct sets specific for largely nonoverlapping pools antigenic determinants represented cell-associated (heat-killed monocytogenes) are generated after infection. We have used models prediction cell epitopes based on primary structure LLO, synthetic amphipathic peptides were evaluated vitro immunogenes vivo. Infection several mice (H-2k H-2d) with monocytogenes resulted could respond consistently two peptides, 215-234 354-371. Mouse lacking expression I-E molecules (e.g., B10.A(4R) C57BL/6) responded but not tested. With C3HeB/FeJ mice, antibodies I-Ek blocked presentation 215-234. The importance N-terminal portion evidenced drastic reduction activity truncated 221-234 224-234). 215-234, strongest most consistent activator from monocytogenes-immune fit well some ways. It be predicted form an alpha-helix, it contained multiple "Rothbard motifs" (charged residue glycine, three hydrophobic amino acids then glycine polar residue), had net charge +2, correct spacing (five six residues basic acid) characteristic I-Ek-binding peptides. Immunization 8 10 recognized immunizing peptide vitro, such only poorly LLO. Our results indicate important target stimulation CD4+ monocytogenes-specific cells, antigenically dominant mice.