Precursor Abundance Influences Divergent Antigen-Specific CD8 T Cell Responses after Yersinia pseudotuberculosis Foodborne Infection.

Primary infection of C57BL/6 mice with the bacterial pathogen Yersinia pseudotuberculosis elicits an unusually large H-2K-restricted CD8 T cell response to the endogenous and protective bacterial epitope YopE. To better understand the basis for this large response, the model OVA epitope was inserted into YopE in Y. pseudotuberculosis and antigen-specific CD8 T cells in mice were characterized after foodborne infection with the resulting strain. The epitope YopE elicited significantly larger CD8 T cell populations in the small intestine, mesenteric lymph nodes (MLNs), spleen, and liver between 7 and 30 days postinfection, despite residing in the same protein and having an affinity for H-2K similar to that of OVA. YopE-specific CD8 T cell precursors were ∼4.6 times as abundant as OVA-specific precursors in the MLNs, spleens, and other lymph nodes of naive mice, explaining the dominance of YopE over OVA at early infection times. However, other factors contributed to this dominance, as the ratio of YopE-specific to OVA-specific CD8 T cells increased between 7 and 30 days postinfection. We also compared the YopE-specific and OVA-specific CD8 T cells generated during infection for effector and memory phenotypes. Significantly higher percentages of YopE-specific cells were characterized as short-lived effectors, while higher percentages of OVA-specific cells were memory precursor effectors at day 30 postinfection in spleen and liver. Our results suggest that a large precursor number contributes to the dominance and effector and memory functions of CD8 T cells generated in response to the protective YopE epitope during Y. pseudotuberculosis infection of C57BL/6 mice.