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J Clin Invest. 2006 May;116(5):1212-5.

An immunologic homunculus for type 1 diabetes.

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  • 1Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado, USA.


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.

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