ACQUIRED-IMMUNITY TO AN INTRACELLULAR PATHOGEN - IMMUNOLOGICAL RECOGNITION OF L-MONOCYTOGENES-INFECTED CELLS

Listeria monocytogenes (L. monocytogenes) is a pathogenic bacterium, a nd subclinical infection in mice is utilized as a prototypic model to investigate the development and expression of acquired resistance to f acultative intracellular organisms. A key virulence factor of L. monoc ytogenes is the hemolysin listeriolysin O (LLO), and BALB/c mice immun ized with hemolysin-secreting strains of L. monocytogenes develop spec ific acquired resistance, while mice immunized with hemolysin-negative strains or non-viable preparations of L. monocytogenes do nt develop a protective immune response. Adoptive transfer studies show that L. m onocytogenes immune CD8(+) T cells mediate acquired resistance. The L. monocytogenes-immune CD8(+) population is cytotoxic, and target cells infected with hemolysin-secreting strains of L. monocytogenes are lys ed, while target cells infected with hemolysin-negative strains or non -viable preparations of L. monocytogenes are nor lysed. MHC class Ia a nd Ib molecules present L. monocytogenes-derived peptides, and we have identified Qa-Ib, a T-region encoded MHC class Ib molecule, as a rest riction element for L. monocytogenes-specific CD8(+) CTL. MHC class Ib -restricted CTL are stimulated following infection with L, monocytogen es and are a significant component of the total MHC class I-restricted CTL population. These findings support the observation that cytoplasm ic L. monocytogenes-derived antigens are endogenously processed and pr esented in association with MHC class Ia and Ib molecules to CD8(+) ef fector cells, and that both populations of effector cells contribute t o the immune response to this intracellular pathogen.