Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease whose onset is believed to be triggered by unknown environmental factors acting on a predisposing genetic background. Islet-infiltrating T(IIT) cells from two IDDM patients, who had died at the onset of the disease from brain swelling as a complication of ketoacidosis, were analysed. The results provided evidence for the involvement of a pancreatic islet cell membrane-bound superantigen as a diabetes aetiopathogenetic factor. There was a selective expansion of a T-cell receptor (TCR) variable segment of the β-chain (Vβ7) in these IIT cells in association with unselected Vα-chain segments; extensive junctional diversity of the TCR Vβ7 chains; and evidence of positive selection, after exposure to diabetic islet cell membrane preparations, of Vβ7+ T-cell clones among peripheral blood lymphocytes from non-diabetic individuals.
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