Autoimmune diseases such as the diabetes that develops in NOD mice depend on immunologic recognition of specific autoantigens, but recognition can result in a pathogenic or protective T cell response. A study by Du et al. in this issue of the JCI demonstrates that TGF-beta signaling by T cells recognizing the insulin peptide B:9-23 is essential for such protection and that this inhibitory cytokine functions in both a paracrine and an autocrine manner (see the related article beginning on page 1360). We propose that the insulin peptide B:9-23 and a conserved TCR motif form an "immunologic homunculus" underlying the relatively common targeting of insulin by T cells that, as demonstrated by the study of Du and coworkers, results in a protective T cell response, or diabetes, as shown by other investigators, for related T cell receptors.