A Protective Epitope in Type III Effector YopE Is a Major CD8 T Cell Antigen during Primary Infection with Yersinia pseudotuberculosis

Abstract

ABSTRACTVirulence in human-pathogenicYersiniaspecies is associated with a plasmid-encoded type III secretion system that translocates a set of Yop effector proteins into host cells. One effector, YopE, functions as a Rho GTPase-activating protein (GAP). In addition to acting as a virulence factor, YopE can function as a protective antigen. C57BL/6 mice infected with attenuatedYersinia pestisgenerate a dominant H2-Kb-restricted CD8 T cell response to an epitope in the N-terminal domain of YopE (YopE69-77), and intranasal vaccination with the YopE69-77peptide and the mucosal adjuvant cholera toxin (CT) elicits CD8 T cells that are protective against lethal pulmonary challenge withY. pestis. Because YopE69-77is conserved in manyYersiniastrains, we sought to determine if YopE is a protective antigen forYersinia pseudotuberculosisand if primary infection with this enteric pathogen elicits a CD8 T cell response to this epitope. Intranasal immunization with the YopE69-77peptide and CT elicited a CD8 T cell response that was protective against lethal intragastricY. pseudotuberculosischallenge. The YopE69-77epitope was a major antigen (∼30% of splenic CD8 T cells were specific for this peptide at the peak of the response) during primary infection withY. pseudotuberculosis, as shown by flow cytometry tetramer staining. Results of infections withY. pseudotuberculosisexpressing catalytically inactive YopE demonstrated that GAP activity is dispensable for a CD8 T cell response to YopE69-77. Determining the features of YopE that are important for this response will lead to a better understanding of how protective CD8 T cell immunity is generated againstYersiniaand other pathogens with type III secretion systems.