This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The immune system is remarkable in its ability to mount responses against a wide array of antigens and to respond with enhanced vigor to antigens encountered in the past. This exaggerated recall immune response or immune memory is a central concept in immunology and it forms the basis of vaccination against infectious diseases. Immune memory is mediated by memory lymphocytes that persist in the host long after resolution of the infection or antigenic insult. To study immune memory, we have developed a novel and powerful transgenic mouse model system. In this system, both effector and memory pools of T lymphocytes are indelibly tagged with the marker, human placental alkaline phosphatase (PLAP) by an irreversible genetic recombination event. Our long-range goal is to understand how immune memory is generated, regulated and maintained. The objective of this application, which is the first step in pursuit of this goal, is to further validate the transgenic mouse model system and to ask fundamental questions about how CD8 T cell memory is generated. The central hypothesis of this application is that antigen-specific effector and memory CD8 T cells can be unambiguously identified. We will use this model system to probe lymphocytic choriomeningitis (LCMV) virus-induced immune responses and the differentiation pathway of immune memory generation. It is our expectation that the resultant approaches will identify key events involved in the generation of CD8 T cell memory. The research will be of significance because what is learned from these studies will contribute to broader understanding of how vaccines that provide long-term protective immunity can be rationally designed.
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