GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE313nnn/GSE313272/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE313272GEOGSEfalseAtomistic TCR-ligand interactions instruct memory T-cell differentiation and crossreactivity [RNA-seq]While memory T-cells provide protective immunity against specific pathogens, their post-encounter differentiation into central (TCM) and/or effector (TEM) subpopulations remains enigmatic. We thus explored the CD8 T-cell receptor (TCR) repertoire of 242 murine TCRαβ clonotypes directed against an immunodominant influenza A virus (IAV) peptide/major histocompatibility complex (pMHC) ligand, the nucleoprotein NP366-374/Db, leveraging single-cell transcriptomics with paired TCR sequencing, mechanosensing metrics, and in vivo memory development plus TCR-pMHC structural analyses. Polar TEM and more variegated TCM repertoires as well as bipotential “bipolar” clonotypes (TBP) revealed weak force-dependent bonding parameters associated with heterosubtypic IAV crossreactivities. TCM and TEM polarities manifest pMHC binding skewed to TCRβ- versus TCRα-subunit mechanotransduction, respectively, unlike the more signaling-balanced TBP TCRs. In sum, TCR diversity anticipates pathogen evolution whereas divergent signaling regulates memory fate.2026/08/05GSE313272GSM9365086GSM9365087GSM9365088GSM9365089GSM9365093GSM9365094GSM9365084GSM9365095GSM9365085GSM9365090GSM9365091GSM936509234290313272Mus musculus