CIITA Gene

The CIITA gene (CIITA stands for: "Class II Major Histocompatibility Complex Transactivator") is a protein coding gene located on chromosome 16p13.13. The CIITA gene encodes a protein with an acidic transcription activation domain, 4 LRRs (leucine rich repeats) and a GTP binding domain.

The encoded protein, class II major histocompatibility complex transactivator, is located in the nucleus and acts as a positive regulator of transcription of class II major histocompatibility complex genes and is referred to as the "master control factor" for expression of these genes. Several transcript variants encoding different isoforms have been found for the CIITA gene.

The protein also binds GTP and uses GTP binding to facilitate its own transport into the nucleus. In the nucleus, the protein does not bind DNA but uses intrinsic acetyltransferase (AT) activity to act as a "co-activator." Alternatively, it can activate HLA class II transcription by modifying proteins that bind to the MHC class II promoter.

Mutations in this gene have been associated with bare lymphocyte syndrome type II (also known as hereditary MHC class II deficiency or HLA class II-deficient combined immunodeficiency), increased susceptibility to rheumatoid arthritis, multiple sclerosis, and possibly heart attack.

Diseases associated with CIITA include:

• Bare Lymphocyte Syndrome, Type II (OMIM: 209920)
• and
• rheumatoid arthritis.

Related pathways include interferon gamma signaling and type II interferon signaling (IFNG).

1. Accolla RS et al (1985) Reactivation by a trans-acting factor of human major histocompatibility complex Ia gene expression in interspecies hybrids between an Ia-negative human B-cell variant and an Ia-positive mouse B-cell lymphoma. Proc Nat Acad Sci 82: 5145-5149.
2. Baxter-Lowe LA et al (1989) HLA gene amplification and hybridization analysis of polymorphism: HLA matching for bone marrow transplantation of a patient with HLA-deficient severe combined immunodeficiency syndrome. J Clin Invest 84: 613-618.
3. Benichou B et al (1991) Class II-antigen-negative patient and mutant B-cell lines represent at least three, and probably four, distinct genetic defects defined by complementation analysis. Proc Nat Acad Sci 88: 4285-4288.
4. Clement LT et al (1988) M. Bare lymphocyte syndrome: consequences of absent class II major histocompatibility antigen expression for B lymphocyte differentiation and function. J Clin Invest 81: 669-675.
5. de la Salle H et al (1999) HLA class I deficiencies. In: Ochs HD et al (eds): Primary Immunodeficiency Diseases: A Molecular and Genetic Approach. New York: Oxford University Press 1999:181-188.