Numerous genomic loci have been implicated in autoimmune disorders, but attempts to identify causal variants, and thereby disease mechanisms, have been hampered by strong linkage disequilibrium; leaving most loci unresolved and the potential of GWAS largely unfulfilled. To overcome this, we developed a massively-parallel reporter assay for use in primary CD4 T-cells, a key effector of many autoimmune diseases, and sought to resolve potential causal variants via their functional effects. This provided testable hypotheses into disease mechanisms, which we illustrate using a multi-disease-associated locus on chromosome 6. By investigating the lead expression-modulating SNP, we uncover an NF-κB-driven regulatory circuit which constrains T-cell activation through the dynamic formation of a super-enhancer that upregulates expression of TNFAIP3 (A20), a key NF-κB inhibitor. In activated T-cells, this circuit is disrupted - and super-enhancer formation prevented - by the risk variant at the lead SNP, thus revealing a molecular mechanism that predisposes to multiple autoimmune diseases.