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The Unveiling of Hidden T‐Cell Determinants of a Native Antigen by Defined Mediators of Inflammation: Implications for the Pathogenesis of Autoimmunity
Author(s) -
Jiang X.,
Moudgil K. D.
Publication year - 2006
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2006.01748.x
Subject(s) - epitope , immunology , autoimmunity , biology , cytokine , antigen , immune system , immunogen , t cell , antigen presentation , antibody , monoclonal antibody
A major hypothesis for the induction of autoimmunity invokes the enhanced display of previously hidden (cryptic) epitopes under inflammatory conditions leading to the activation of self‐reactive T cells. However, there is meager data that directly validate the influence of specific immune mediators on the upregulation of the presentation of cryptic determinants in vivo . We tested the effect on well‐defined cryptic epitopes of hen eggwhite lysozyme (HEL) of the availability locally of a cytokine (IL‐2, IL‐4, IL‐6, IL‐10, TNF‐α or granulocyte‐macrophage colony‐stimulating factor) at the antigen delivery site, or of the pretreatment of the immunogen with a cathepsin (Cat B, D, L or S) prior to use in vivo . Each of the three mouse strains (H‐2 b/d/k ) tested revealed a unique profile of T‐cell reactivity to different cryptic epitopes of HEL in response to a particular cytokine or cathepsin. These results provide proof of principle for the reversal of crypticity of self‐epitopes by immune mediators in the local milieu. Moreover, co‐immunization with an antigen and a cytokine offers a simple and reliable tool for studying the role of cryptic epitopes in autoimmunity. Our results also strengthen the rationale for the use of inhibitors of cytokine/cathepsin activity in the treatment of autoimmune diseases.