CD4 ⁺ T cell fate is independent of TCR specificity. (a) Frequency and sizes of clonotypes amongst gp66:I-A^b-specific CD4⁺ T cells. (b) Proportion of cells with a T_H1, T_FH, or pT_CM phenotype for each expanded clonotype (≥5 cells). Each row represents an individual clonotype. Clonotypes are ordered by hierarchical clustering with complete linkage and correlation distance. (c) Diffusion map of gp66:I-A^b+ CD4⁺ T cells overlaid with the five largest clonotypes for each clonotype-phenotype pattern. (d) Proportion of clonotypes (≥5 cells) exhibiting bias toward a particular T_H cell lineage. Clonotypes exhibiting no lineage bias are labeled as “mixed.” (e) Observed number of clonotypes with cells distributed across the T_FH, T_H1, and T_CM phenotypes indicated along the x axis. (f) Shared gene signatures representing T_H lineages across two independent experiments identifying matched clusters. Pearson correlation between transcriptomes of replicate gp66:I-A^b-specific CD4⁺ T cell clusters demonstrating high concordance between independent samples. (g) Shared clonotypes with distinct phenotypes in biological replicate samples. Each depicted clonotype has ≥5 cells and an overlap in TCRα, TCRβ, or paired TCRα/TCRβ sequences across replicate samples. Matching clonotypes between replicate samples indicated by black shading. Shared paired TCRα and TCRβ CDR3 sequences, but distinct phenotypes across replicate samples (clonotype 44 [replicate 2], and clonotypes 4, 74, and 16 [replicate 1]) are indicated by an asterisk. (h) CDR3 sequences and T_H lineage bias for clonotypes with a shared TCR specificity group across the two biological replicate samples.