Antigen processing patterns determine GAD65-specific regulation vs. pathogenesis

Front Biosci (Landmark Ed). 2009 Jan 1;14:344-51. doi: 10.2741/3248.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Gene Knockout Techniques
  • Glutamate Decarboxylase / immunology*
  • Humans
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Glutamate Decarboxylase
  • glutamate decarboxylase 2