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

Publikation

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

Wissenschaftlicher Artikel/Review - 15.03.2001

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

Bereiche

Medizinisches Forschungszentrum, Institut für Immunbiologie

PubMed

11238607

Zitation

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.

Art

Wissenschaftlicher Artikel/Review (Englisch)

Zeitschrift

Journal of immunology (Baltimore, Md. : 1950) 2001; 166

Veröffentlichungsdatum

15.03.2001

ISSN (Druck)

0022-1767

Seiten

3678-87

Kurzbeschreibung/Zielsetzung

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.