HZI Kolloquium mit Veit Buchholz
The smallest unit: How single T cells generate adaptive immune responses
A core feature of protective T cell responses to infection is the robust expansion and diversification of naïve epitope-specific T cell populations into short-lived effector and long-lived memory subsets. By in vivo fate mapping we recently found that immune responses to acute primary and recall infection derived from single CD8+ T cells are highly variable, and that robust acute and recall immunity is established as a population average, requiring the recruitment of multiple epitope-specific precursors. Subjecting these datasets to unbiased mathematical modeling identified a progressive differentiation framework, in which slowly proliferating memory precursors differentiate into rapidly expanding short-lived subsets. We now investigate how this framework is modulated by extrinsic factors like antigen or inflammation and how immune responses derived from single T cells are maintained in the face of chronic infection. Overall, these data provide insights into how complex biological systems implement stochastic processes to guarantee robust outcomes.
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