The endogenous antigen-specific CD8+ T cell repertoire is composed of unbiased and biased clonotypes with differential fate commitments
Leena Abdullah, Francesco E Emiliani, Chinmay M Vaidya, Hannah Stuart, Shawn C Musial, Fred W Kolling, Joshua J Obar, Pamela C Rosato, Margaret E Ackerman, Li Song, Aaron McKenna, Yina H Huang
Understanding how diverse CD8+ T cell populations differentiate into effector and memory cells is a central question in immunology. Using CARLIN lineage recording combined with single-cell RNA and TCR sequencing, we tracked endogenous antigen-specific CD8 T cells during acute viral infection.
We identified several hundred T cell receptor (TCR) clonotypes that constitute the polyclonal response against a single antigen, and discovered most clonotypes showed strong preferences toward either memory or effector development. These intrinsic biases were neither random nor easily overridden by environmental factors.
Gene expression analysis revealed cell fate divergence occurred early during effector development. Notably, memory-biased clonotypes retain their fate preferences in subclonal populations, but effector-biased subclones can switch to a memory fate.
Overall, the polyclonal CD8+ T cell response consists of populations with varying degrees of flexibility in responding to environmental signals during immune differentiation.