A CIITA-independent pathway that promotes expression of endogenous rather than exogenous peptides in immune-privileged sites

Eur J Immunol. 2004 Feb;34(2):471-80. doi: 10.1002/eji.200324195.

Abstract

A CIITA-independent pathway of MHC class II expression has been found in the eye and the brain, both immune-privileged sites. Although corneal endothelial cells were unable to express MHC class II in response to IFN-gamma alone, these cells readily expressed MHC class II molecules via a CIITA-independent pathway when triggered by simultaneous exposure to IFN-gamma and TNF-alpha. CIITA-independent expression of MHCclass II molecules enabled corneal endothelial cells to present cytosolic, but not endosomal, ovalbumin (OVA) to OVA-primed T cells. To determine whether CIITA-independent expression of MHC class II is relevant in vivo, minor H-only-incompatible corneal allografts prepared from CIITA knockout (KO) mice, MHC class II KO mice or wild-type donors were placed in eyes of normal mice. Cornea allografts from wild-type and CIITA KO mice suffered similar rejection fates, whereas far fewer class II-deficient corneas were rejected. In addition, MHC class II-bearing macrophages were observed in cuprizone-induced inflammatory and demyelinating brain lesions of CIITA KO mice. We conclude that class II expression via the CIITA-independent pathway enhances the vulnerability to rejection of corneal grafts expressing minor antigens. The potential relevance of CIITA-independent MHC class II expression at immune-privileged sites is discussed in relation to tolerance to strong autoantigens.

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / metabolism
  • Antigens, Differentiation, B-Lymphocyte / immunology
  • Brain / cytology
  • Brain / immunology*
  • Cornea / cytology
  • Cornea / immunology*
  • Corneal Transplantation / immunology
  • Endothelial Cells
  • Endothelium / cytology
  • Endothelium / immunology
  • Flow Cytometry
  • Genes, MHC Class II / immunology
  • Histocompatibility Antigens Class II / biosynthesis*
  • Histocompatibility Antigens Class II / immunology
  • Interferon-gamma / immunology
  • Interferon-gamma / pharmacology
  • Interleukin-2 / biosynthesis
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nuclear Proteins / genetics
  • Nuclear Proteins / immunology*
  • Trans-Activators / genetics
  • Trans-Activators / immunology*
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation

Substances

  • Antigens, Bacterial
  • Antigens, Differentiation, B-Lymphocyte
  • H antigen
  • Histocompatibility Antigens Class II
  • Interleukin-2
  • MHC class II transactivator protein
  • Nuclear Proteins
  • Trans-Activators
  • Tumor Necrosis Factor-alpha
  • invariant chain
  • Interferon-gamma