A CIITA-independent pathway that promotes expression of endogenous rather than exogenous peptides in immune-privileged sites.
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.
Arancibia-Cárcamo
Carolina V
CV
Schepens Eye Research Institute, Harvard Medical School, Boston, USA. arancibia@rics.bwh.harvard.edu
Osawa
Hideya
H
Arnett
Heather A
HA
Háskova
Zdenka
Z
George
Andrew J T
AJ
Ono
Santa J
SJ
Ting
Jenny P-Y
JP
Streilein
J Wayne
JW
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D001921:Brain / Q000166:cytology / Q000276:immunology*; D003315:Cornea / Q000166:cytology / Q000276:immunology*; D016039:Corneal Transplantation / Q000276:immunology; D042783:Endothelial Cells; D004727:Endothelium / Q000166:cytology / Q000276:immunology; D005434:Flow Cytometry; D005802:Genes, MHC Class II / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology; D015854:Up-Regulation
D000942:Antigens, Bacterial; D000944:Antigens, Differentiation, B-Lymphocyte; C022863:H antigen; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; C045084:invariant chain; D007371:Interferon-gamma