Retinoic acid induction of major histocompatibility complex class I genes in NTera-2 embryonal carcinoma cells involves induction of NF-kappa B (p50-p65) and retinoic acid receptor beta-retinoid X receptor beta heterodimers.

Retinoic acid (RA) treatment of human embryonal carcinoma (EC) NTera-2 (NT2) cells induces expression of major histocompatibility complex (MHC) class I and beta-2 microglobulin surface molecules. We found that this induction was accompanied by increased levels of MHC class I mRNA, which was attributable to the activation of the two conserved upstream enhancers, region I (NF-kappa B like) and region II. This activation coincided with the induction of nuclear factor binding activities specific for the two enhancers. Region I binding activity was not present in undifferentiated NT2 cells, but binding of an NF-kappa B heterodimer, p50-p65, was induced following RA treatment. The p50-p65 heterodimer was produced as a result of de novo induction of p50 and p65 mRNAs. Region II binding activity was present in undifferentiated cells at low levels but was greatly augmented by RA treatment because of activation of a nuclear hormone receptor heterodimer composed of the retinoid X receptor (RXR beta) and the RA receptor (RAR beta). The RXR beta-RAR beta heterodimer also bound RA responsive elements present in other genes which are likely to be involved in RA triggering of EC cell differentiation. Furthermore, transfection of p50 and p65 into undifferentiated NT2 cells synergistically activated region I-dependent MHC class I reporter activity. A similar increase in MHC class I reporter activity was demonstrated by cotransfection of RXR beta and RAR beta. These data show that following RA treatment, heterodimers of two transcription factor families are induced to bind to the MHC enhancers, which at least partly accounts for RA induction of MHC class I expression in NT2 EC cells.

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Developmental and tissue-specific expression of nuclear proteins that bind the regulatory element of the major histocompatibility complex class I gene.

Journal of Experimental Medicine ◽

10.1084/jem.169.4.1309 ◽

1989 ◽

Vol 169 (4) ◽

pp. 1309-1321 ◽

Cited By ~ 46

Author(s):

P A Burke ◽

S Hirschfeld ◽

Y Shirayoshi ◽

J W Kasik ◽

K Hamada ◽

...

Keyword(s):

Gene Expression ◽

Mhc Class I ◽

Regulatory Element ◽

Binding Activity ◽

Class I ◽

Specific Expression ◽

Enhancer Activity ◽

Region I ◽

Region Ii ◽

I Gene

Expression of MHC class I genes varies according to developmental stage and type of tissues. To study the basis of class I gene regulation in tissues in vivo, we examined binding of nuclear proteins to the conserved cis sequence of the murine H-2 gene, class I regulatory element (CRE), which contains two independent factor-binding sites, region I and region II. In gel mobility shift analyses we found that extracts from adult tissues that express class I genes, such as spleen and liver, had binding activity to region I. In contrast, extracts from brain, which does not express class I genes, did not show region I binding activity. In addition, fetal tissues that express class I gene at very low levels, also did not reveal region I binding activity. Binding activity to region I became detectable during the neonatal period when class I gene expression sharply increases. Most of these tissues showed binding activity to region II, irrespective of class I gene expression. Although region II contained a sequence similar to the AP-1 recognition site, AP-1 was not responsible for the region II binding activity detected in this work. These results illustrate a correlation between region I binding activity and developmental and tissue-specific expression of MHC class I genes. The CRE exerts an enhancer-like activity in cultured fibroblasts. We evaluated the significance of each factor binding to CRE. Single 2-bp mutations were introduced into the CRE by site-directed mutagenesis and the ability of each mutant to elicit the enhancer activity was tested in transient CAT assays. A mutation that eliminated region I protein binding greatly impaired enhancer activity. A mutation that eliminated region II binding also caused a lesser but measurable effect. We conclude that region I and region II are both capable of enhancing transcription of the class I gene. These results indicate that in vivo regulation of MHC class I gene expression is mediated by binding of trans-acting factors to the CRE.

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Specific suppression of major histocompatibility complex class I and class II genes in astrocytes by brain-enriched gangliosides.

Journal of Experimental Medicine ◽

10.1084/jem.178.4.1357 ◽

1993 ◽

Vol 178 (4) ◽

pp. 1357-1363 ◽

Cited By ~ 35

Author(s):

P T Massa

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class I ◽

Class Ii ◽

Binding Activity ◽

Inducible Expression ◽

Class I ◽

Mrna Levels ◽

Major Histocompatibility ◽

Ifn Gamma ◽

Histocompatibility Complex

The effect of brain-enriched gangliosides on constitutive and cytokine-inducible expression of major histocompatibility complex (MHC) class I and II genes in cultured astrocytes was studied. Before treatment with gangliosides, astrocytes expressed constitutive MHC class I but not class II molecules, however, the expression of both MHC class I and II cell surface molecules on astrocytes was induced to high levels by interferon gamma (IFN-gamma). Constitutive and IFN-gamma-inducible expression of MHC class I and II molecules was suppressed by treatment of astrocytes with exogenous bovine brain gangliosides in a dose-dependent manner. Constitutive and induced MHC class I and II mRNA levels were also suppressed by gangliosides, indicating control through transcriptional mechanisms. This was consistent with the ability of gangliosides to suppress the binding activity of transcription factors, especially NF-kappa B-like binding activity, important for the expression of both MHC class I and II genes. These studies may be important for understanding mechanisms of central nervous system (CNS)-specific regulation of major histocompatibility molecules in neuroectodermal cells and the role of gangliosides in regulating MHC-restricted antiviral and autoimmune responses within the CNS.

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TNF stimulates expression of mouse MHC class I genes by inducing an NF kappa B-like enhancer binding activity which displaces constitutive factors.

The EMBO Journal ◽

10.1002/j.1460-2075.1989.tb08556.x ◽

1989 ◽

Vol 8 (12) ◽

pp. 3793-3800 ◽

Cited By ~ 166

Author(s):

A. Israël ◽

O. Le Bail ◽

D. Hatat ◽

J. Piette ◽

M. Kieran ◽

...

Keyword(s):

Mhc Class I ◽

Binding Activity ◽

Class I ◽

Nf Kappa B

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Ligand Design for Specific MHC Class I Molecules on the Cell Surface

10.26434/chemrxiv.12865688 ◽

2020 ◽

Author(s):

Xizheng Sun ◽

Reika Tokunaga ◽

Yoko Nagai ◽

Ryo Miyahara ◽

Akihiro Kishimura ◽

...

Keyword(s):

Cell Surface ◽

Mhc Class I ◽

Targeted Delivery ◽

Peptide Ligands ◽

Class I ◽

Class I Mhc ◽

Mhc I ◽

Histocompatibility Complex ◽

High Binding Affinity ◽

Mhc Class I Molecules

<p><a></a><a></a><a>We have validated that ligand peptides designed from antigen peptides could be used for targeting specific major histocompatibility complex class I (MHC-I)</a> molecules on cell surface. To design the ligand peptides, we used reported antigen peptides for each MHC-I molecule with high binding affinity. From the crystal structure of the peptide/MHC-I complexes, we determined a modifiable residue in the antigen peptides and replaced this residue with a lysine with an ε-amine group modified with functional molecules. The designed ligand peptides successfully bound to cells expressing the corresponding MHC-I molecules via exchange of peptides bound to the MHC-I. We demonstrated that the peptide ligands could be used to transport a protein or a liposome to cells expressing the corresponding MHC-I. The present strategy may be useful for targeted delivery to cells overexpressing MHC-I, which have been observed autoimmune diseases.</p>

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DIAGNOSIS AND TREATMENT OF ACUTE REJECTION CAUSED BY DONOR SPECIFIC ANTI-MICA ANTIBODY IN A HIGHLY SENSITIZED, PEDIATRIC RENAL TRANSPLANT RECIPIENT (MAJOR-HISTOCOMPATIBILITY-COMPLEX (MHC) CLASS-I RELATED CHAIN A ANTIGEN)

Transplantation Journal ◽

10.1097/01.tp.0000330900.18399.05 ◽

2008 ◽

Vol 86 (Supplement) ◽

pp. 622-623

Author(s):

S Narayan ◽

E Tsai ◽

J Q. Zhang ◽

E Reed ◽

R Ettenger

Keyword(s):

Major Histocompatibility Complex ◽

Renal Transplant ◽

Transplant Recipient ◽

Acute Rejection ◽

Renal Transplant Recipient ◽

Mhc Class I ◽

Class I ◽

Diagnosis And Treatment ◽

Histocompatibility Complex ◽

Pediatric Renal Transplant

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Transcription of non-classic major histocompatibility complex (MHC) class I in the bovine placenta throughout gestation and after Brucella abortus infection

Veterinary Immunology and Immunopathology ◽

10.1016/j.vetimm.2015.06.014 ◽

2015 ◽

Vol 167 (3-4) ◽

pp. 166-170

Author(s):

Larissa Sarmento dos Santos ◽

Juliana Pinto da Silva Mol ◽

Auricélio Alves de Macedo ◽

Ana Patrícia Carvalho Silva ◽

Diego Luiz dos Santos Ribeiro ◽

...

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class I ◽

Brucella Abortus ◽

Class I ◽

Major Histocompatibility ◽

Bovine Placenta ◽

Histocompatibility Complex

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Major histocompatibility complex class I molecules mediate association of SV40 with caveolae.

Molecular Biology of the Cell ◽

10.1091/mbc.8.1.47 ◽

1997 ◽

Vol 8 (1) ◽

pp. 47-57 ◽

Cited By ~ 174

Author(s):

E Stang ◽

J Kartenbeck ◽

R G Parton

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class I ◽

Mammalian Cells ◽

Simian Virus 40 ◽

Class I ◽

Major Histocompatibility ◽

Surface Binding ◽

Histocompatibility Complex ◽

Mhc Class I Molecule ◽

Mhc Class I Molecules

Simian virus 40 (SV40) has been shown to enter mammalian cells via uncoated plasma membrane invaginations. Viral particles subsequently appear within the endoplasmic reticulum. In the present study, we have examined the surface binding and internalization of SV40 by immunoelectron microscopy. We show that SV40 associates with surface pits which have the characteristics of caveolae and are labeled with antibodies to the caveolar marker protein, caveolin-1. SV40 is believed to use major histocompatibility complex (MHC) class I molecules as cell surface receptors. Using a number of MHC class I-specific monoclonal antibodies, we found that both viral infection and association of virus with caveolae were strongly reduced by preincubation with anti-MHC class I antibodies. Because binding of SV40 to MHC class I molecules may induce clustering, we investigated whether antibody cross-linked class I molecules also redistributed to caveolae. Clusters of MHC class I molecules were indeed shown to be specifically associated with caveolin-labeled surface pits. Taken together, the results suggest that SV40 may make use of MHC class I molecule clustering and the caveolae pathway to enter mammalian cells.

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