TCR avidity governs CD8 T cell competitive fitness in an antigen dose-dependent manner but does not reliably predict fate

T cell receptor (TCR) avidity for cognate peptide–MHC (pMHC) has been proposed to influence both the magnitude and differentiation of CD8 T cell responses, but its effects have been difficult to isolate from confounding factors such as epitope specificity and antigen presentation kinetics. To address this, we generated TCR-transgenic mice (CoVT1lo and CoVT1hi) expressing low- or high-avidity receptors for the same conserved H2-Kb–restricted epitope (VVLSFELL) derived from SARS-CoV-1/2 Spike. We show that TCR avidity governs expansion and differentiation through distinct mechanisms. Higher avidity consistently confers a competitive advantage only when antigen is abundant, with inter-clonal competition increasing in a dose-dependent manner. In contrast, the impact of avidity on differentiation varied with inflammatory context: across peptide vaccines, mRNA vaccination, and viral infection, higher avidity was associated with divergent effector versus memory precursor outcomes. These findings support a model in which TCR avidity determines competitive fitness in an antigen-dependent manner, whereas fate decisions integrate avidity with context-specific innate signals. Overall design: vaccine_1, vaccine_2, and vaccine_3, are biological replicates of immunized C57BL/6 mice followed by isolation of CD8+ T cells enriched and sorted from the spleen 7 days post-immunization; naive_1, naive_2, and naive_3 are biological replicates of C57BL/6 mice of isolated CD8+ T cells enriched and via sorted from the spleen