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

Primary infection of C57BL/6 mice with the bacterial pathogen Yersinia pseudotuberculosis elicits an unusually large H-2K^b-restricted CD8⁺ T cell response to the endogenous and protective bacterial epitope YopE_69-77. To better understand the basis for this large response, the model OVA_257-264 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_69-77 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^b similar to that of OVA_257-264. 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_69-77 over OVA_257-264 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_69-77 epitope during Y. pseudotuberculosis infection of C57BL/6 mice.