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

Infect Immun. 2021 Jul 15;89(8):e0026521. doi: 10.1128/IAI.00265-21. Epub 2021 Jul 15.

Abstract

Primary infection of C57BL/6 mice with the bacterial pathogen Yersinia pseudotuberculosis elicits an unusually large H-2Kb-restricted CD8+ T cell response to the endogenous and protective bacterial epitope YopE69-77. To better understand the basis for this large response, the model OVA257-264 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 YopE69-77 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-2Kb similar to that of OVA257-264. 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 YopE69-77 over OVA257-264 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 YopE69-77 epitope during Y. pseudotuberculosis infection of C57BL/6 mice.

Keywords: CD8+ T cell response; bacterial infection; precursor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Disease Models, Animal
  • Epitopes, T-Lymphocyte / immunology
  • Host-Pathogen Interactions / immunology*
  • Immunologic Memory
  • Mice
  • Mice, Inbred C57BL
  • T-Cell Antigen Receptor Specificity*
  • Yersinia pseudotuberculosis / immunology*
  • Yersinia pseudotuberculosis Infections / immunology*
  • Yersinia pseudotuberculosis Infections / microbiology*
  • Yersinia pseudotuberculosis Infections / transmission

Substances

  • Antigens, Bacterial
  • Epitopes, T-Lymphocyte