CIITA is a human gene which encodes a protein called the class II, major histocompatibility complex, transactivator. [5] Mutations in this gene are responsible for the bare lymphocyte syndrome in which the immune system is severely compromised and cannot effectively fight infection. [5] Chromosomal rearrangement of CIITA is involved in the pathogenesis of Hodgkin lymphoma and primary mediastinal B cell lymphoma. [6]
CIITA mRNA can only be detected in human leukocyte antigen (HLA) system class II-positive cell lines and tissues. This highly restricted tissue distribution suggests that expression of HLA class II genes is to a large extent under the control of CIITA. [7] However, CIITA does not appear to directly bind to DNA. [7] Instead CIITA functions through activation of the transcription factor RFX5. [8] Hence CIITA is classified as a transcriptional coactivator.
The CIITA protein contains an acidic transcriptional activation domain, 4 LRRs (leucine-rich repeats) and a GTP binding domain. [9] The protein uses GTP binding to facilitate its own transport into the nucleus. [10] Once in the nucleus, the protein acts as a positive regulator of class II major histocompatibility complex gene transcription, and is often referred to as the "master control factor" for the expression of these genes. [11] [12]
CIITA expression is induced by interferon gamma, possibly assisted by other signals. [13] MHC II expression in intestinal epithelial cells is upregulated under inflammation. [13]
CIITA has been shown to interact with:
The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are called MHC molecules.
A class II gene is a type of gene that codes for a protein. Class II genes are transcribed by RNAP II.
Bare lymphocyte syndrome type II is a rare recessive genetic condition in which a group of genes called major histocompatibility complex class II are not expressed. The result is that the immune system is severely compromised and cannot effectively fight infection.
Bare lymphocyte syndrome is a condition caused by mutations in certain genes of the major histocompatibility complex or involved with the processing and presentation of MHC molecules. It is a form of severe combined immunodeficiency.
MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, and B cells. These cells are important in initiating immune responses.
Nuclear transcription factor Y subunit beta is a protein that in humans is encoded by the NFYB gene.
HLA class I histocompatibility antigen, alpha chain F is a protein that in humans is encoded by the HLA-F gene. It is an empty intracellular molecule that encodes a non-classical heavy chain anchored to the membrane and forming a heterodimer with a β-2 microglobulin light chain. It belongs to the HLA class I heavy chain paralogues that separate from most of the HLA heavy chains. HLA-F is localized in the endoplasmic reticulum and Golgi apparatus, and is also unique in the sense that it exhibits few polymorphisms in the human population relative to the other HLA genes; however, there have been found different isoforms from numerous transcript variants found for the HLA-F gene. Its pathways include INF-gamma signaling and CDK-mediated phosphorylation and removal of the Saccharomycescerevisiae Cdc6 protein, which is crucial for functional DNA replication.
HLA class II histocompatibility antigen, DM beta chain is a protein that in humans is encoded by the HLA-DMB gene.
MHC class II regulatory factor RFX1 is a protein that, in humans, is encoded by the RFX1 gene located on the short arm of chromosome 19.
DNA-binding protein RFX5 is a protein that in humans is encoded by the RFX5 gene.
Lymphocyte-activation gene 3, also known as LAG-3, is a protein which in humans is encoded by the LAG3 gene. LAG3, which was discovered in 1990 and was designated CD223 after the Seventh Human Leucocyte Differentiation Antigen Workshop in 2000, is a cell surface molecule with diverse biologic effects on T cell function. It is an immune checkpoint receptor and as such is the target of various drug development programs by pharmaceutical companies seeking to develop new treatments for cancer and autoimmune disorders. In soluble form it is also being developed as a cancer drug in its own right.
DNA-binding protein RFXANK is a protein that in humans is encoded by the RFXANK gene.
Regulatory factor X-associated protein is a protein that in humans is encoded by the RFXAP gene.
DNA-binding protein RFX2 is a protein that in humans is encoded by the RFX2 gene.
Transcription factor RFX4 is a protein that in humans is encoded by the RFX4 gene.
Zinc finger and BTB domain-containing protein 32 is a protein that in humans is encoded by the 1960 bp ZBTB32 gene. The 52 kDa protein is a transcriptional repressor and the gene is expressed in T and B cells upon activation, but also significantly in testis cells. It is a member of the Poxviruses and Zinc-finger (POZ) and Krüppel (POK) family of proteins, and was identified in multiple screens involving either immune cell tumorigenesis or immune cell development.
HLA class II histocompatibility antigen, DX beta chain is a protein that in humans is encoded by the HLA-DQB2 gene.
Transcriptional repressor NF-X1 is a protein that in humans is encoded by the NFX1 gene.
Transcription factor RFX3 is a protein that in humans is encoded by the RFX3 gene.
Zinc finger, X-linked, duplicated family member C (ZXDC) is a human CIITA-binding protein involved in the activation of major histocompatibility complex (MHC) class I and II. For binding to occur, ZXDC must form an oligomeric complex with another copy of itself or with ZXDA, a related protein. ZXDC is activated by sumoylation, a post-translational modification.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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