Nonsecreted bacterial proteins induce recall CD8 T cell responses but do not serve as protective antigens

Secreted or nonsecreted Ag expressed by recombinant Listeria monocytogenes can prime CD8 T cells. However, Ag-specific memory CD8 T cells confer protection against bacteria secreting Ag, but not against bacteria expressing the nonsecreted form of the same Ag. This dichotomy may be explained by a long-standing hypothesis that nonsecreted Ags are less effective than secreted Ags at inducing a protective immune response at the onset of infection. We tested this hypothesis by examining whether these two different forms of Ag induce different primary and secondary CD8 T cell responses. The primary responses to secreted and nonsecreted Ags expanded and contracted almost synchronously, although the responses to nonsecreted Ags were of lower magnitude. These results demonstrate that the kinetics of the CD8 T cell response are similar regardless of whether Ag is accessible to the endogenous MHC class I pathway or can only be presented through cross-presentation. No differences were detected in the CD8 T cell recall response to L monocytogenes expressing secreted or nonsecreted Ags. Nonsecreted Ags are as effective as secreted Ags at the induction of a rapid recall response by memory CD8 T cells. Thus, the inability of nonsecreted bacterial proteins to serve as protective Ags cannot be attributed to a defective CD8 T cell response.