Insulin A-chain autoreactive T cells identified from newly diagnosed Type 1 diabetic patients 

Janos Kis1, 2, Peter Engelmann1, 3, Geoffrey Richman1, Heyam Jalahej1, Tihamer Orban1
1 Section of Immunology and Immunogenetics Joslin Diabetes Center, Harvard Medical School, Boston, MA  02215 USA
2 Department of Internal Medicine and Gastroenterology, Polyclinic of the Hospitaller Brothers Budapest, 1027 Hungary
3 Department of Immunology and Biotechnology, Faculty of Medicine, University of Pecs, 7643 Hungary

T1DM is characterized by the T cell dependent destruction of the insulin producing pancreatic beta cells in humans. The list of target candidates is still increasing, even though there is no clear consensus regarding to the nature of the pivotal antigen. One of the most verisimilar autoantigens is the insulin or the proinsulin. Full length insulin in high dose can not be used by interventional studies, because it has metabolic effects, therefore the identification of the exact epitope is crucial. 
The authors hypothesized that autoreactive T cells can be identified from newly diagnosed T1DM patients. Six newly diagnosed T1DM patients and 6 healthy individuals were involved in the study. Peripheral mononuclear blood cells were cultured at the presence of various antigens. Fifteen aminoacid long insulin peptides, GAD protein, full insulin B chain, and tetanus toxoid as positive control were applied as stimulatory compounds. T cell activation was assessed by thymidine incorporation. Indeed, tetanus toxoid caused high proliferation capacity in lymphocytes. Among the diabetic related antigens the highest activation was observed by overlapping insulin peptides, which contained the first 5 amino-acids of the A chain. 
The results suggest that the candidate epitope is expressed on the insulin A chain. It is essential to identify the pivotal autoantigen of T1DM then it can be used successfully in tissue specific intervention studies to halt or delay the disease progression.

Insulin A-chain autoreactive T cells identified from newly diagnosed type 1 diabetic patients