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Eomes broadens the scope of CD8 T cell memory by inhibiting apoptosis in low-affinity cells

ABSTRACT: The memory CD8 T cell pool must select for high-affinity clones to efficiently counter re-infection yet must retain a level of clonal diversity to allow recognition of pathogens with mutated immuno-dominant epitopes. How this is mediated is unclear, especially in the context of a selective drive for antigen-affinity. We find that low-affinity memory exclusively depends on the transcription factor Eomes in the first days after antigen encounter. Eomes is induced at low activating signal strength and directly drives transcription of the pro-survival protein Bcl-2. At higher signal intensity T-bet is induced which suppresses Bcl-2, generating a survival advantage for low-affinity cells. High-affinity cells form memory independent of Eomes and have a proliferative advantage over low-affinity cells, which compensates for their survival deficit. Thus, we demonstrate on a molecular level how sufficient diversity of the memory pool is established in an environment of affinity-based selection.

ORGANISM(S): Mus musculus

PROVIDER: GSE118174 | GEO | 2020/08/01

REPOSITORIES: GEO

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Eomes broadens the scope of CD8 T cell memory by inhibiting apoptosis in low-affinity cells

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