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

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

Ludewig Burkhard, Hengartner H, Melief C J, Toes R E, Odermatt B, Dumrese T, Ochsenbein A F, Pericin M, McCoy K, Zinkernagel R M

Units

Medizinisches Forschungszentrum, Institute of Immunobiology

PubMed

11238607

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.