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. This proposal will examine the interplay of TCR avidity with other biological properties of CD8+ cytotoxic T-lymphocytes (CTL) that may be important in immune defense - migration, proliferation and acquisition of different effector functions. In principle, these properties may be independent of each other (stochastic diversification). Alternatively, they could be orchestrated by one property (e.g., TCR avidity and/or differentiation status of the cell ?na?ve, effector or memory). Experiments proposed here will evaluate which of the CTL properties may be critically important for immune defense in vivo, and whether and to what extent these properties may be coordinated in their expression.
The aims will ask:
Aim 1. Is the variation in CTL migration, proliferation and function influenced by TCR avidity in na?ve, effector and memory T-cell subsets? Aim 2 What is the role of variation in individual CTL properties ?avidity, migration, proliferation and function ?in immune defense against HSV-1 in vivo? These studies should provide novel insights into the fundamental biology of an efficient CTL response in vivo, and pave the way for manipulation of its efficacy in infectious diseases in general as well as in specific protection against ocular and CNS manifestations of the corneal HSV infection.
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