Genetic studies have revealed that autoimmune susceptibility variants are over-represented in memory CD4⁺ T cell regulatory elements^1–3. Understanding how genetic variation affects gene expression in different T cell physiological states is essential for deciphering genetic mechanisms of autoimmunity^4,5. Here we characterized the dynamics of genetic regulatory effects at eight time points during memory CD4⁺ T cell activation with high depth RNA-seq in healthy individuals. We discovered widespread dynamic allele-specific expression across the genome, where the balance of alleles changes over time. These genes were four-fold enriched within autoimmune loci. We found pervasive dynamic regulatory effects within six HLA genes. HLA-DQB1 alleles had one of three distinct transcriptional regulatory programs. Using CRISPR/Cas9 genomic editing we demonstrated that a promoter variant is causal for T cell-specific control of HLA-DQB1 expression. Our study shows that genetic variation in cis regulatory elements affects gene expression in a lymphocyte activation status-dependent manner contributing to the inter-individual complexity of immune responses.