Cytotoxic-T-lymphocyte responses to epitopes of listeriolysin O and p60 following infection with Listeria monocytogenes

Abstract

In order to test the influence of the cell surface density of a specific H2-Kd-presented epitope on the subsequent level of the cytotoxic-T-lymphocyte (CTL) response directed against the epitope, we investigated the CTL response to two secreted products of Listeria monocytogenes from mice immunized with viable L. monocytogenes. We determined the response to the H2-Kd-presented amino acid 91 to 99 (aa91-99) immunodominant peptide of listeriolysin O (LLO) and to the aa217-225 immunodominant peptide of p60. The p60-derived peptide appears at the cell surface as an H2-Kd-complexed peptide at a level sixfold higher than that of LLO aa91-99. CTL frequency analysis of anti-LLO- or anti-p60-specific CTLs from mice immunized with wild-type L. monocytogenes showed that the numbers of immune spleen cell-derived CTLs specific for the two peptides were essentially equivalent. We have also found that Listeria-specific CTL populations lyse target cells pulsed with the p60 aa217-225 peptide with a magnitude of the lytic response markedly less than that for targets pulsed with the LLO aa91-99 peptide. Additionally, immunization with mutants of L. monocytogenes which do not stimulate anti-LLO-specific CTLs does not alter the CTL frequency of anti-p60-specific effector cells, with levels of anti-p60-specific CTLs similar to those seen in mice immunized with wild-type L. monocytogenes. These results suggest that the relative cell surface density of major histocompatibility complex class I-presented L. monocytogenes-derived epitopes is but one of the criteria which determine the magnitude of the cytotoxic effector cell response that develops in antilisterial immunity.