Existing antilisterial immunity does not inhibit the development of a Listeria monocytogenes-specific primary cytotoxic T-lymphocyte response

Infection of BALB/c mice with Listeria monocytogenes stimulates an antilist erial immune response evident by the appearance of H2-K-d-restricted CD8(+) cytotoxic T lymphocytes (CTLs) specific for the nanomer peptides amino aci ds (aa) 91 to 99 of listeriolysin O (LLO 91-99) and aa 217 to 225 of the p6 0 molecule (p60 217-225), We have introduced point mutations at anchor resi dues within LLO 91-99 (92F) or p60 217-225 (218F), and BALB/c mice infected with L. monocytogenes strains containing these point mutations do not deve lop CTLs specific for LLO 91-99 or p60 217-225, respectively. We have used these strains to test whether primary CTL responses against L, monocytogene s-derived determinants can be stimulated within an environment of existing antilisterial immunity. We found that the development of a primary L, monoc ytogenes-specific CTL response is not altered by existing immunity to L. mo nocytogenes, For example, primary immunization with the p60 218F strain of L, monocytogenes followed by a secondary immunization with wild-type L. mon ocytogenes results in stimulation of p60 217-225-specific CTLs at primary r esponse levels and LLO 91-99-specific effecters at levels consistent with a memory CTL response. Similarly, primary immunization with the 92F strain o f L. monocytogenes followed by a secondary immunization with wild-type L, m onocytogenes results in stimulation of LLO 91-99-specific CTLs at primary r esponse levels and p60 217-225-specific effecters at levels consistent with a memory CTL response. These results provide additional support for the us e of L. monocytogenes as a recombinant vaccine vector and show that antivec tor immunity does not inhibit the development of a primary CTL response whe n the epitope is delivered by L. monocytogenes as the vaccine strain.