The adaptor molecule BCAP is essential for the formation of CD8+ T cell memory

Abstract

Abstract Generation of effector and memory CD8+ T cells is pivotal for the clearance of intracellular infections and forms the basis for vaccination strategies against a wide range of pathogens and anti-cancer immunotherapy. We have generated novel data which shows that the signaling scaffold protein B cell adaptor for PI3-kinase (BCAP) is upregulated in activated CD8+ T cells, links TCR/CD3 engagement to the PI3K signaling cascade and is essential for CD8+ T cell memory formation. To analyze the cell intrinsic properties of BCAP in CD8+ T cells, we used OT-1+ mice which have a high affinity CD8+ T Cell Receptor (TCR) for the ova peptide. We transferred 5,000 WT OT-1+CD45.1+cells and 5,000 BCAPKO OT-1+CD45.2+ cells into CD45.1+CD45.2+ recipients, then infected with Listeria Monocytogenes expressing the ova peptide. We found that BCAP is essential for the proper clonal expansion of CD8+ T cells and BCAP deficiency in CD8+ T cells resulted in a loss of KLRG1+CD127− Terminal Effector Cells (TECs) in favor of KLRG1− CD127+ Memory Precursor Cells (MPCs) in vivo. Strikingly, we observed an enhanced CD8+ T cell contraction phenotype in BCAP deficient CD8+ T cells which led to a significant loss of antigen-specific memory CD8+ T cells. BCAPKO CD8+ T cells were undetectable in 50% of all mice analyzed at day 100 post infection. Therefore BCAP is critical for the formation of CD8+ T cell memory. We found the greatest loss of cells was confined to the recently described KLRG1+CD27loCXCR3loEomeslo effector memory cells, which have potent cytolytic function and anti-cancer capabilities. Finally we found that the ability of BCAPKO memory CD8+ T cells to respond to secondary infection was dysregulated. To conclude, BCAP is essential for the formation of CD8+ T cell memory.