The development of antigen-specific therapeutics for autoimmune disease is highly attractive but drug developers face several hurdles. Coeliac disease is a prevalent chronic immune illness with an exceptionally strong disease HLA class II association, where the causative gluten peptides have been well defined. A peptide-based therapy designed on this knowledge offered the promise of such a targeted tolerogenic approach and the idea was bolstered by promising findings from first-in-man Phase 1 trials. However, the global Phase 2 trial did not meet its primary endpoint in the therapy protecting coeliac patients from gluten-induced symptoms. Fortunately, there is a silver lining: the study informed the development of a novel antigen-specific immunomonitoring approach based on interleukin-2 production that is now also the basis of a novel companion diagnostic tool and symptom biomarker. The advent of a simple but sensitive tool to track gluten-specific T cells is facilitating pre-clinical and clinical drug development in coeliac disease with multiple novel therapies now in Phase 1 and 2 trials.