A Chlamydia trachomatis Strain Expressing Ovalbumin Stimulates an Antigen-Specific CD4⁺ T Cell Response in Mice

Antigen-specific CD4⁺ T cells against Chlamydia are crucial for driving bacterial clearance and mediating protection against reinfection. Although the Chlamydia trachomatis protein Cta1 has been identified to be a dominant murine CD4⁺ T cell antigen, its level of expression during the bacterial developmental cycle and precise localization within the host cell are unknown. Newly developed tools for Chlamydia genetic manipulation have allowed us to generate a C. trachomatis strain expressing a heterologous CD4⁺ T cell epitope from ovalbumin (OVA) consisting of OVA residues 323 to 339 (OVA_323-339). By tagging proteins expressed in C. trachomatis with OVA_323-339, we can begin to understand how protein expression, developmental regulation, and subcellular compartmentalization affect the potential of those proteins to serve as antigens. When OVA_323-339 was expressed as a fusion with green fluorescent protein, we found that we were able to elicit an OT-II T cell response in an antigen-dependent manner, but surprisingly, these T cells were unable to reduce bacterial burden in mice. These data suggest that the subcellular localization of antigen, the level of antigen expression, or the timing of expression within the developmental cycle of Chlamydia may play a crucial role in eliciting a protective CD4⁺ T cell response.