The two novel MHC class II transactivators RFX5 and CIITA both control expression of HLA-DM genes

Kern, Ilse; Steimle, Viktor; Siegrist, Claire‐Anne; Mach, Bernard

doi:10.1093/intimm/7.8.1295

Cited by 98 publications

(50 citation statements)

References 22 publications

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“…24 The promoters of HLA class II and related genes share a set of conserved sequence elements, the W/S, X1, X2 and Y boxes, which interact with transcription factors (TF) including members of the regulatory factor X (RFX) family, the nuclear factor Y and the cAMP-responsive element binding protein CREB. 25,26 All these TF and co-factors bind to cis regulatory elements of the HLA class II promoters to form a highly stable multimeric complex known as MHC enhanceosome. Due to their ubiquitous expression, the enhanceosome components fail to account for the cell type specificity and/or IFNg inducibility of HLA class II antigen expression.…”

Section: Regulation Of Hla Class II Antigen Expressionmentioning

confidence: 99%

HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

2017

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The human leukocyte antigen (HLA) class II antigen-processing machinery (APM) presents to cognate CD4 C T-cells antigenic peptides mainly generated from exogeneous proteins in the endocytic compartment. These CD4 C T cells exert helper function, but may also act as effector cells, thereby recognizing HLA class II antigen-expressing tumor cells. Thus, HLA class II antigen expression by tumor cells influences the tumor antigen (TA)-specific immune responses and, depending on the cancer type, the clinical course of the disease. Many types of human cancers express HLA class II antigens, although with marked differences in their frequency. Some types of cancer lack HLA class II antigen expression, which could be due to structural defects or deregulation affecting different components of the complex HLA class II APM and/or from lack of cytokine(s) in the tumor microenvironment. In this review, we have summarized the information about HLA class II antigen distribution in normal tissues, the structural organization of the HLA class II APM, their expression and regulation in malignant cells, the defects, which have been identified in malignant cells, and their functional and clinical relevance.

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Section: Regulation Of Hla Class II Antigen Expressionmentioning

confidence: 99%

HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

2017

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“…Expression of all these genes is constitutive in APC cells, and can be induced by IFN-g in other cell types (Barr and Saunders, 1991;Brown et al, 1993;Chang and Flavell, 1995;Collins et al, 1984;Kern et al, 1995). At the molecular level, Ii and HLA-DM promoters have the S-X-Y motifs found upstream of class II genes that are essential for both constitutive and IFN-g-induced expression (Brown et al, 1991(Brown et al, , 1993Radley et al, 1994;Westerheide et al, 1997), and activation of these promoters is mediated by the class II master regulator, CIITA (Chang and Flavell, 1995;Kern et al, 1995). To determine if IFN-g-induction of the mouse Ii and H2-Ma loci requires pRB, expression of these genes was assessed in IFN-g-treated RB +/+ and RB 7/7 MEFs by RT ± PCR.…”

Section: Ifn-g-induction Of II and H2-m Is Prb-independentmentioning

confidence: 99%

pRB is required for interferon-γ-induction of the MHC class II Aβ gene

Zhu¹,

Pattenden

Bremner

1999

Oncogene

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pRB is required for IFN-g-induction of MHC class II in human tumor cell lines, providing a potential link between tumor suppressors and the immune system. However, other genes, such as cyclin D1, show pRBdependency only in tumor cells, so by analogy, pRB may not be necessary for cII-regulation in normal cells. Here, we demonstrate that induction of the mouse MHC class II I-A heterodimer is normal in RB +/+ mouse embryonic ®broblasts (MEFs), but de®cient in RB 7/7 MEFs. Inducibility is restored in RB 7/7 MEFs stably transfected with wild type RB cDNA or infected with an adenovirus expressing pRB. Thus, involvement of pRB in MHC class II expression is conserved in the mouse and is not an aberrant feature of tumorigenic, aneuploid, human tumor cells. Although cII genes are generally induced in a coordinate fashion, suggesting a common mechanism, we found that pRB was speci®cally required for induction of the Ab, but not Aa or other MHC cII genes including Eb, Ii and H2-Ma. Finally, IFN-ginduction of class II transactivator (CIITA), was pRBindependent, suggesting that pRB works downstream of this master-regulator of MHC class II expression.

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“…CIITA expression appears to be a nearly absolute requisite for expression of class II MHC, whether constitutive or inducible (17,19,23,47,85,103,114,118,119). A number of class II MHC-related genes including genes encoding HLA-DM (H-2M in mice) and invariant chain (Ii), with promoters similar to those for classical class II genes, are also regulated by CIITA (17,18,22,23,50,137). CIITA can also upregulate expression of class I MHC genes and beta-2-microglobulin (␤ 2 m) through effects at site ␣ in addition to X-and Y-like sequences in the promoters for these genes (40,72,104).…”

Section: Introductionmentioning

confidence: 99%

Class II Transactivator: Mastering the Art of Major Histocompatibility Complex Expression

Harton

Ting

2000

Molecular and Cellular Biology

194

166

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The two novel MHC class II transactivators RFX5 and CIITA both control expression of HLA-DM genes

Cited by 98 publications

References 22 publications

HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

pRB is required for interferon-γ-induction of the MHC class II Aβ gene

Class II Transactivator: Mastering the Art of Major Histocompatibility Complex Expression

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