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

J Immunol. 2001 Mar 15;166(6):3678-87. doi: 10.4049/jimmunol.166.6.3678.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation* / genetics
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology*
  • Antigens, Viral / metabolism*
  • Cytotoxicity, Immunologic / genetics
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / transplantation
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / pathology
  • Glycoproteins / immunology
  • Glycoproteins / metabolism
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Injections, Subcutaneous
  • Insulin / genetics
  • Islets of Langerhans / immunology
  • Islets of Langerhans / pathology
  • Lymphocyte Activation* / genetics
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Peptides / immunology*
  • Peptides / metabolism*
  • Promoter Regions, Genetic / genetics
  • Promoter Regions, Genetic / immunology
  • Rats
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology
  • Tumor Cells, Cultured / transplantation
  • Viral Proteins*

Substances

  • Antigens, Viral
  • Glycoproteins
  • Histocompatibility Antigens Class I
  • Insulin
  • Peptide Fragments
  • Peptides
  • Viral Proteins
  • glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus