Publication

Rapid peptide turnover and inefficient presentation of exogenous antigen critically limit the activation of self-reactive CTL by dendritic cells

Journal Paper/Review - Mar 15, 2001

Units
PubMed

Citation
Ludewig B, Hengartner H, Melief C, Toes R, Odermatt B, Dumrese T, Ochsenbein A, Pericin M, McCoy K, Zinkernagel R. Rapid peptide turnover and inefficient presentation of exogenous antigen critically limit the activation of self-reactive CTL by dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 2001; 166:3678-87.
Type
Journal Paper/Review (English)
Journal
Journal of immunology (Baltimore, Md. : 1950) 2001; 166
Publication Date
Mar 15, 2001
Issn Print
0022-1767
Pages
3678-87
Brief description/objective

This study evaluated to what extent presentation of exogenously acquired self-Ags via MHC class I molecules on DC might contribute to the activation of self-reactive CTL and subsequent development of autoimmune disease. We show here by using the rat insulin promotor lymphocytic choriomeningitis virus glycoprotein model of autoimmune diabetes that the activation of self-reactive CTL by DC after uptake of exogenous Ag is very limited, first by the short half-life of MHC class I-associated peptides on DC in vitro and in vivo, and second by the rather inefficient MHC class I presentation of cell-associated self-Ags by DC. These two mechanisms are probably crucial in establishing high thresholds for the induction of self-reactive CTL that prevent autoimmune sequelae after release of sequestered and previously immunologically ignored tissue Ags.