Immune repertoire sequencing of UCB naive T-cell subsets

T cell receptor (TCR) repertoire analysis provides crucial insight into the maturation of the adaptive immune system. In this study, we examined TCR diversity and structure in functional T cell subsets from umbilical cord blood (UCB) at very early gestation (25 weeks) through to adulthood. Using TCRen prediction, we observed that preterm naive CD8+ TCRs exhibited a higher binding affinity to viral epitopes, indicating an intrinsic bias toward recognizing common viral antigens during early development. UCB-derived naive regulatory CD4+ T cells also exhibited TCR repertoire features that differed from adult Tregs indicating developmental differences at the level of TCR selection. Notably, our data showed a developmental shift in TCR repertoire formation-from germline-driven selection during the fetal period, characterized by strong CDR2-MHC interactions, to more antigen-driven and CDR3-diverse repertoires after birth. Together, these results provide new insight into the ontogeny of immune repertoire formation and the unique roles of T cell subsets in early life.