A CIITA-independent pathway that promotes expression of endogenous rather than exogenous peptides in immune-privileged sites
| Autor: | Hideya Osawa, Jenny P.-Y. Ting, J. Wayne Streilein, Heather A. Arnett, Santa Jeremy Ono, Carolina V. Arancibia-Cárcamo, Andrew J.T. George, Z Haskova |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Transcription Genetic Immunology Antigen presentation Genes MHC Class II chemical and pharmacologic phenomena Major histocompatibility complex Cornea Corneal Transplantation Interferon-gamma Mice Immune system Antigen MHC class I CIITA Immunology and Allergy Animals Endothelium Mice Knockout MHC class II Antigens Bacterial Mice Inbred BALB C biology Tumor Necrosis Factor-alpha Histocompatibility Antigens Class II Brain Endothelial Cells Nuclear Proteins Flow Cytometry Cell biology Up-Regulation Transplantation Antigens Differentiation B-Lymphocyte Mice Inbred C57BL biology.protein Trans-Activators Interleukin-2 |
| Zdroj: | European journal of immunology. 34(2) |
| ISSN: | 0014-2980 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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