IMR Press / FBL / Volume 14 / Issue 1 / DOI: 10.2741/3248

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Antigen processing patterns determine GAD65-specific regulation vs. pathogenesis
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1 Division of Immune Regulation, Torrey Pines Institute for Molecular Studies, La Jolla, California 92121, USA.
Academic Editor:Antonio Cava
Front. Biosci. (Landmark Ed) 2009, 14(1), 344–351;
Published: 1 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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