Rapid peptide turnover and inefficient presentation of exogenous antigen critically limit the activation of self-reactive CTL by dendritic cells |
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Authors: | Ludewig B McCoy K Pericin M Ochsenbein A F Dumrese T Odermatt B Toes R E Melief C J Hengartner H Zinkernagel R M |
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Institution: | Institute of Experimental Immunology, Department of Pathology, University of Zürich, Zürich, Switzerland. ludewigb@pathol.unizh.ch |
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Abstract: | 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. |
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