Class II transactivator regulates the expression of multiple genes involved in antigen presentation.

CIITA (a major histocompatibility complex [MHC] class II transactivator) has been shown to be required for the expression of MHC class II genes in both B cells and interferon gamma-inducible cells. Here we demonstrate that CIITA not only activates MHC class II genes but also genes required for antigen presentation. Mutant HeLa cells, defective in the expression of classic MHC class II genes, invariant chain, and the newly described human histocompatibility leukocyte antigen-DM genes, were used to study the role of CIITA in the regulation of these genes. Upon transfection with CIITA cDNA, the mutant cells expressed all three genes, suggesting that CIITA is a global regulator for the expression of genes involved in antigen presentation.

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The Role of the MHC Class II Transactivator in Class II Expression and Antigen Presentation by Astrocytes and in Susceptibility to Central Nervous System Autoimmune Disease

The Journal of Immunology ◽

10.4049/jimmunol.169.12.6720 ◽

2002 ◽

Vol 169 (12) ◽

pp. 6720-6732 ◽

Cited By ~ 58

Author(s):

Olaf Stüve ◽

Sawsan Youssef ◽

Anthony J. Slavin ◽

Chelsea L. King ◽

Juan Carlos Patarroyo ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Autoimmune Disease ◽

Antigen Presentation ◽

Mhc Class Ii ◽

Class Ii ◽

Class Ii Transactivator ◽

Mhc Class Ii Transactivator

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The MHC Class II Transactivator CIITA: Not (Quite) the Odd-One-Out Anymore among NLR Proteins

International Journal of Molecular Sciences ◽

10.3390/ijms22031074 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1074

Author(s):

Jorge Alfonso León Machado ◽

Viktor Steimle

Keyword(s):

Gene Expression ◽

Mhc Class Ii ◽

Protein Interactions ◽

Transcriptional Regulator ◽

Class Ii ◽

Class Ii Transactivator ◽

Mhc I ◽

Mhc Ii ◽

Mhc Class Ii Transactivator

In this review, we discuss the major histocompatibility complex (MHC) class II transactivator (CIITA), which is the master regulator of MHC class II gene expression. CIITA is the founding member of the mammalian nucleotide-binding and leucine-rich-repeat (NLR) protein family but stood apart for a long time as the only transcriptional regulator. More recently, it was found that its closest homolog, NLRC5 (NLR protein caspase activation and recruitment domain (CARD)-containing 5), is a regulator of MHC-I gene expression. Both act as non-DNA-binding activators through multiple protein–protein interactions with an MHC enhanceosome complex that binds cooperatively to a highly conserved combinatorial cis-acting module. Thus, the regulation of MHC-II expression is regulated largely through the differential expression of CIITA. In addition to the well-defined role of CIITA in MHC-II GENE regulation, we will discuss several other aspects of CIITA functions, such as its role in cancer, its role as a viral restriction element contributing to intrinsic immunity, and lastly, its very recently discovered role as an inhibitor of Ebola and SARS-Cov-2 virus replication. We will briefly touch upon the recently discovered role of NLRP3 as a transcriptional regulator, which suggests that transcriptional regulation is, after all, not such an unusual feature for NLR proteins.

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