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Induction of MHC class I expression by the MHC class II transactivator CIITA
B K Martin1, K C Chin, J C Olsen
1Lineberger Comprehensive Cancer Center, Department of Microbiology-Immunology, University of North Carolina at Chapel Hill, 27599-7295, USA.
Insights
The MHC class II transactivator (CIITA) can induce Major Histocompatibility Complex (MHC) class I expression, even in cells lacking MHC class I. This indicates CIITA plays a crucial role in regulating MHC class I gene induction.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Major Histocompatibility Complex (MHC) molecules are crucial for immune responses.
- MHC class I expression is tightly regulated.
- The role of MHC class II transactivator (CIITA) in MHC class I regulation was unclear.
Purpose of the Study:
- To investigate the role of CIITA in the induction of MHC class I surface expression.
- To identify the DNA elements involved in CIITA-mediated MHC class I transactivation.
Main Methods:
- Utilized MHC class I-deficient cell lines.
- Assessed MHC class I gene and surface expression.
- Examined the effect of CIITA and its variants on MHC class I promoter activity.
- Investigated the role of the site alpha DNA element.
Main Results:
- CIITA was found to induce surface expression of MHC class I molecules.
- CIITA targets the promoter of MHC class I heavy chain genes, specifically the site alpha DNA element.
- Interferon-gamma (IFNγ)-induced MHC class I expression also requires an intact site alpha.
- A cell line defective in CIITA induction failed to upregulate MHC class I in response to IFNγ.
- Trans-dominant-negative CIITA forms reduced MHC class I promoter function and surface expression.
Conclusions:
- CIITA plays a significant role in the induction of MHC class I gene expression.
- The site alpha DNA element is a key target for CIITA-mediated regulation of MHC class I.
- CIITA's function is essential for both basal and IFNγ-induced MHC class I expression.
Abstract:
Major histocompatibility complex (MHC) class I-deficient cell lines were used to demonstrate that the MHC class II transactivator (CIITA) can induce surface expression of MHC class I molecules. CIITA induces the promoter of MHC class I heavy chain genes. The site alpha DNA element is the target for CIITA-induced transactivation of class I. In addition, interferon-gamma (IFNgamma)-induced MHC class I expression also requires an intact site alpha. The G3A cell line, which is defective in CIITA induction, does not induce MHC class I antigen and promoter in response to IFNgamma. Trans-dominant-negative forms of CIITA reduce class I MHC promoter function and surface antigen expression. Collectively, these data argue that CIITA has a role in class I MHC gene induction.