Inhibition of altered peptide ligand-mediated antagonism of human GAD65-responsive CD4+ T cells by non-antagonizable T cells

✍ Scribed by John A. Gebe; Susan A. Masewicz; Sharon A. Kochik; Helena Reijonen; Gerald T. Nepom

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 259 KB
• Volume: 34
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200425535

✦ Synopsis

Abstract

Altered peptide ligands derived from T cell‐reactive self antigens have been shown to be protective therapeutic agents in animal models of autoimmunity. In this study we identified several altered peptide ligands derived from the type 1 diabetes‐associated autoantigen human glutamic acid decarboxylase 65 (hGAD65) epitope that were capable of antagonizing a subset of a panel of human CD4^+^ GAD65 (555–567)‐responsive T cell clones derived from a diabetic individual. While no altered peptide ligand was able to antagonize all six clones in the T cell panel, a single‐substituted peptide of isoleucine to methionine at position 561, which resides at the TCR contact p5 position, was able to antagonize five out of the six hGAD65‐responsive clones. In a mixed T cell culture system we observed that altered peptide ligand‐mediated antagonism is inhibited in a dose‐dependent manner by the presence of non‐antagonizable hGAD65 (555–567)‐responsive T cells. From an analysis of the cytokines present in the mixed T cell cultures, interleukin‐2 was sufficient to inhibit altered peptide ligand‐induced antagonism. The inhibition of altered peptide ligand‐mediated antagonism of self‐antigen‐responsive T cells by non‐antagonizable T cells has implications in altered peptide ligand therapy where T cell antagonism is the goal.