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The endogenous antigen-specific CD8+ T cell repertoire is composed of unbiased and biased clonotypes with differential fate commitment.

ABSTRACT: Generating balanced populations of CD8+ effector and memory T cells is necessary for immediate and durable immunity to infections and cancer. Yet, a definitive understanding of how a diverse CD8+ T cell repertoire differentiates remains unclear. We identified several hundred TCR clonotypes that constitute the polyclonal response against a single antigen and found that a majority of TCR clonotypes were highly biased towards memory or effector fate. TCR-intrinsic biases were not stochastic and were dominant over environmental cues. Differential gene expression analysis of memory- or effector-biased TCR clonotypes showed bifurcation of differential fates at the early effector stage. Additionally, phylogenetic analysis revealed that memory-biased clonotypes retain their fate preferences in subclonal populations but effector-biased subclones can switch to memory fate. Our study highlights that the polyclonal CD8+ T cell response is a composite of unbiased and biased clonotypes with varying capacity to incorporate environmental cues in their cell fate decisions.

ORGANISM(S): Mus musculus

PROVIDER: GSE241403 | GEO | 2025/02/27

REPOSITORIES: GEO

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The endogenous antigen-specific CD8+ T cell repertoire is composed of unbiased and biased clonotypes with differential fate commitment.

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