Altered-peptide ligand has therapeutic activity.(Brief Article)

2002 OCT 2 - (NewsRx.com & NewsRx.net) -- An altered-peptide ligand from an islet beta-cell-specific antigen in type 1 diabetes has been found to have therapeutic activity, report scientists at Neurocrine Bioscience Inc., California, USA.

"The nonobese diabetic (NOD) mouse is a good model for human type 1 diabetes, which is characterized by auto-reactive T cell-mediated destruction of insulin-producing islet beta-cells of the pancreas," the researchers stated.

"The 9-23 amino acid region of the insulin B-chain [B(9-23)] is an immunodominant T-cell target antigen in the NOD mouse that plays a critical role in the disease process. By testing a series of B(9-23) peptide analogs with single or double alanine substitutions, we identified a set of altered peptide ligands (APLs) capable of inhibiting B(9-23)-induced proliferative responses of NOD pathogenic T-cell clones.

"These APLs were unable to induce proliferation of these clones," continued D.G. Alleva and colleagues. "However, vaccinations with the APLs induced strong cellular responses, as measured by in vitro lymphocyte proliferation and Th2 cytokine production (i.e., interleukin [IL]-4 and IL-10, but not T-interferon [IFN-gamma]). These responses were cross-reactive with the native antigen, B(9-23), suggesting that the APL-induced Th2 responses may provide protection by controlling endogenous B(9-23)-specific Th1 (i.e., IFN-gamma-producing) pathogenic responses.

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