Open Access
Antigen processing patterns determine GAD65-specific regulation vs. pathogenesis
Yang D Dai1,Eli E Sercarz1
Division of Immune Regulation, Torrey Pines Institute for Molecular Studies, La Jolla, California 92121, USA.
DOI: 10.2741/3248 Volume 14 Issue 1, pp.344-351
Published: 01 January 2009
(This article belongs to the Special Issue An update on the pathogenesis of immune dysregulation in autoimmunity)

Alterations in presenting self determinants to T cells may depend upon the availability of sites on the molecule adjacent to known determinants to different processing enzymes, or, at the level of amino acid sequence or conformation of a single determinant. We have studied three possible ways that could modulate the processing and presentation of T cell determinants of a diabetes autoantigen, glutamic acid decarboxylase (GAD) 65, which could contribute to induction of GAD65-specific regulatory versus pathogenic T cells in type 1 diabetes (T1D): 1) enhanced presentation of subdominant/cryptic determinants to T cells that have not been well-tolerized, which may activate T cells of high affinity and high aggressiveness; 2) trimming or truncating flanking residues which may otherwise provide needed binding energy to determinants that activate regulatory cells, thus releasing autoaggressive T cells from suppression; 3) biochemical or chemical modifications of self antigens in an inflammatory environment or within activated antigen presenting cells (APC) which may convert a previously regulatory antigen or determinant into a disease-causing one that activates autoreactive T cells at a higher affinity.

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Yang D Dai, Eli E Sercarz. Antigen processing patterns determine GAD65-specific regulation vs. pathogenesis. Frontiers in Bioscience-Landmark. 2009. 14(1); 344-351.