T Cell Memory Generation in the Face of Persistent Antigen Presentation

In the face of emerging infectious diseases, we are challenged to develop innovative vaccine strategies that can protect against rapidly evolving and highly virulent pathogens. Since CD4 T cells are needed to generate and maintain protective B cell and CD8 T cell immunity, new vaccines should ideally elicit both T and B cell memory. In order to generate long-lived immune memory in both T and B cell compartments, such vaccines will need to induce cross-reactive memory against highly conserved antigens within a given pathogen. Acute influenza infection provides a model system whereby the generation of T cell memory is influenced by residual antigen depots. These antigen depots persist for months after live virus clearance, and provide continued, low level T cell stimulation. Here we discuss the impact and implications of residual pathogen-derived antigen depots on the generation and maintenance of T cell immunity. We propose that effective vaccines may need to include persistent depots of conserved proteins to generate a functionally flexible memory T cell pool that can confer protection against rapidly evolving pathogens.