Rapid peptide turnover and inefficient presentation of exogenous antigen critically limit the activation of self-reactive CTL by dendritic cells.
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.
Institute of Experimental Immunology, Department of Pathology, University of Zürich, Zürich, Switzerland. ludewigb@pathol.unizh.ch
B
B
Ludewig
K
K
McCoy
M
M
Pericin
A F
AF
Ochsenbein
T
T
Dumrese
B
B
Odermatt
R E
RE
Toes
C J
CJ
Melief
H
H
Hengartner
R M
RM
Zinkernagel
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D007279:Injections, Subcutaneous; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000276:immunology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000276:immunology; D051381:Rats; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000637:transplantation; D014764:Viral Proteins
D000956:Antigens, Viral; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus