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Limited Model Antigen Expression By Transgenic Fungi Induces Disparate Fates During Differentiation Of Adoptively Transferred T Cell Receptor Transgenic CD4+T Cells: Robust Activation And Proliferation With Weak Effector Function During Recall

Marcel Wüthrich, Karen Ersland, John C. Pick-Jacobs, Benjamin H. Gern, Christopher A. Frye, Thomas D. Sullivan, Meghan B. Brennan, Hanna I. Filutowicz, Kevin O'Brien, Keegan D. Korthauer, Stacey Schultz-Cherry, Bruce S. Klein

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ABSTRACTCD4+T cells are the key players of vaccine resistance to fungi. The generation of effective T cell-based vaccines requires an understanding of how to induce and maintain CD4+T cells and memory. The kinetics of fungal antigen (Ag)-specific CD4+T cell memory development has not been studied due to the lack of any known protective epitopes and clonally restricted T cell subsets with complementary T cell receptors (TCRs). Here, we investigated the expansion and function of CD4+T cell memory after vaccination with transgenic (Tg)Blastomyces dermatitidisyeasts that display a model Ag, Eα-mCherry (Eα-mCh). We report that Tg yeast led to Eα display on Ag-presenting cells and induced robust activation, proliferation, and expansion of adoptively transferred TEa cells in an Ag-specific manner. Despite robust priming by Eα-mCh yeast, antifungal TEa cells recruited and produced cytokines weakly during a recall response to the lung. The addition of exogenous Eα-red fluorescent protein (RFP) to the Eα-mCh yeast boosted the number of cytokine-producing TEa cells that migrated to the lung. Thus, model epitope expression on yeast enables the interrogation of Ag presentation to CD4+T cells and primes Ag-specific T cell activation, proliferation, and expansion. However, the limited availability of model Ag expressed by Tg fungi during T cell priming blunts the downstream generation of effector and memory T cells.