Regulation Of MHC Class Research Articles

NLRC5 deficiency protects against acute kidney injury in mice by mediating carcinoembryonic antigen–related cell adhesion molecule 1 signaling

There is significant progress in understanding the structure and function of NLRC5, a member of the nucleotide oligomerization domain-like receptor family. However, in the context of MHC class I gene expression, the functions of NLRC5 in innate and adaptive immune responses beyond the regulation of MHC class I genes remain controversial and unresolved. In particular, the role of NLRC5 in the kidney is unknown. NLRC5 was significantly upregulated in the kidney from mice with renal ischemia/reperfusion injury. NLRC5 deficient mice significantly ameliorated renal injury as evidenced by decreased serum creatinine levels, improved morphological injuries, and reduced inflammatory responses versus wild type mice. Similar protective effects were also observed in cisplatin-induced acute kidney injury. Mechanistically, NLRC5 contributed to renal injury by promoting tubular epithelial cell apoptosis and reducing inflammatory responses were, at least in part, associated with the negative regulation of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). To determine the relative contribution of NLRC5 expression by parenchymal cells or leukocytes to renal damage during ischemia/reperfusion injury, we generated bone marrow chimeric mice. NLRC5 deficient mice engrafted with wild type hematopoietic cells had significantly lower serum creatinine and less tubular damage than wild type mice reconstituted with NLRC5 deficient bone marrow. This suggests that NLRC5 signaling in renal parenchymal cells plays the dominant role in mediating renal damage. Thus, modulation of the NLRC5-mediated pathway may have important therapeutic implications for patients with acute kidney injury.

The regulatory network behind MHC class I expression

The MHC class I pathway, presenting endogenously derived peptides to T lymphocytes, is hijacked in many pathological conditions. This affects MHC class I levels and peptide presentation at the cell surface leading to immune escape of cancer cells or microbes. It is therefore important to identify the molecular mechanisms behind MHC class I expression, processing and antigen presentation. The identification of NLRC5 as regulator of MHC class I transcription was a huge step forward in understanding the transcriptional mechanism involved. Nevertheless, many questions concerning MHC class I transcription are yet unsolved. Here we illuminate current knowledge on MHC class I and NLRC5 transcription, we highlight some remaining questions and discuss the use of quickly developing high-content screening tools to reveal unknowns in MHC class I transcription in the near future.

Abstract 585: Chromosome 9p24.1 deletions as a determinant of tumor immune surveillance and immune checkpoint blockade therapy in non-small cell lung cancer

Abstract Anti-PD-1/PD-L1 immune checkpoint blockade therapy requires the presence of PD-L1/PD-L2 and MHC class I antigens on the tumor cell surface. We previously found JAK1 truncating mutations in endometrial cancer cells that impairs JAK1/JAK2-STAT1-IRF1-mediated signaling pathway, which regulates MHC class I antigen presentation. To determine the potential role and genetic defects in the IFN-γ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed the Cancer Genome Atlas (TCGA) data. Expression of IRF1 correlated with cytolytic activity markers GZMA and PRF1. Loss-of-function (LOF) genetic alterations in the IFN-γ-IRF1 pathway genes were found in 64 cases (6.3%) among 1016 patients. These genetic defects occurred prevalently in the JAK2 gene (33 cases) and often through deletions (29 cases) of chromosome 9p24.1. JAK2 gene deletions were frequently associated with deletions of CD274 and PDCD1LG2 genes that encode PD-L1 and PD-L2, respectively, whereas CD274 and PDCD1LG2 deletions were always accompanied by JAK2 deletions. Chromosome 9p is frequently deleted in NSCLC. This has been attributed to CDKN2A/CDKN2B and PTPRD tumor suppressor genes located at the chromosome 9p21.3-9p24.1. Interestingly, JAK2, CD274, and PDCD1LG2 genes are co-localized at chromosome 9p24.1 near the CDKN2A/CDKN2B and PTPRD genes. JAK2, CD274, and PDCD1LG2 deletion often but not always coincided with CDKN2A/CDKN2B and PTPRD deletions. IFN-γ induced IRF1 expression and cell surface HLA-ABC levels in A549 cells that contain wildtype JAK2 but not in H1573 cells that had a truncating JAK2. Deletion of JAK2 or inhibition of JAK2 kinase activity in A549 cells resulted in loss of IFN-γ-regulated IRF1 and cell surface HLA-ABC, whereas expression of exogenous JAK2 in H1573 cells restored IFN-γ responses. These findings reveal a previously unrecognized significance of chromosome 9p deletion in NSCLC and point to chromosome 9p24.1 as a determinant of immune checkpoint therapy. Citation Format: Tao Shen, Jie Wu. Chromosome 9p24.1 deletions as a determinant of tumor immune surveillance and immune checkpoint blockade therapy in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 585. doi:10.1158/1538-7445.AM2017-585

Rab11a Regulates MHC Class II Recycling and Promotes Antigenic Peptide Exchange in Recycling Endosomes of Mature Dendritic Cells

Abstract Dendritic cells (DCs) specialize in antigen capture and maintain a highly dynamic pool of peptide-MHC class II complexes (MHC-II) that continuously internalized and degraded in immature DCs. By contrast, in mature DCs pMHC-II internalizes but is efficiently recycled back to the plasma membrane for recognition by CD4 T cells. Regulation of pMHC-II biosynthesis and degradation is essential for optimal DC function, however the molecular basis of pMHC-II recycling and the cellular machinery that orchestrates pMHC-II trafficking are incompletely understood. In the present study we found that internalized pMHC-II on mature DCs, but not immature DCs, colocalizes with the regulator of endosome recycling Rab11a. Using a lentivirus encoded shRNA, we show that Rab11a knock-down inhibits recycling of pMHC-II in mature DCs. Moreover, Rab11a knock-down results in the intracellular accumulation of internalized surface pMHC-II. We also show that Rab11a knock-down in mature DCs specifically inhibits presentation of a “recycling endosome” epitope of internalized influenza hemagglutinin only in mature DCs. Our study thus identifies Rab11a as an important regulator of pMHC-II recycling that can enhance presentation of certain antigenic peptides in mature DCs.

NLRC5 Functions beyond MHC I Regulation-What Do We Know So Far?

NLRC5 is a member of the NLR family that acts as a transcriptional activator of MHC class I genes. In line with the function of several related NLR proteins in innate immune responses, there is, however, also ample evidence that NLRC5 contributes to innate and adaptive immune responses beyond the regulation of MHC class I genes. In human and murine cells, for example, NLRC5 was proposed to contribute to inflammatory and type I interferon responses. The role of NLRC5 in these and other cellular processes is hitherto still not well understood and blurred by discrepancies in the reported data. Here, we provide a detailed and critical discussion of the available experimental data on the emerging biological functions of NLRC5 in innate immune responses in men and mice. Better awareness of the multiple roles of NLRC5 will help to define its overall contribution to immune responses and cancer.

PO-1006 Recipients With In Utero Induction Of Tolerance Up-regulated Mhc Class I In The Engrafted Donor Skin

Background and aims The alterations in MHC class I expression play a crucial step in immune evasion of cancer or virus-infected cells. This study aimed to examine whether tolerized grafts modified MHC class I expression. Methods FVB/N mice were rendered tolerant of C57BL/6 alloantigens by in utero transplantation of C57BL/6 marrows. Postnatally, engrafted donor skins and leukocytes were examined for their MHC expression by quantitative real-time PCR and flow cytometry. Results In this murine tolerance model established by in utero marrow transplantation, engrafted donor skins up-regulated their MHC class I related gene transcripts after short-term (1~2 weeks) or long-term (>1 month) engraftment. This biological phenomenon was simultaneously associated with up-regulation of TAP1 gene transcripts, suggesting an important role of TAP1 in the regulation of MHC class I pathway. Notably, the surface MHC class I molecules of H-2K q in engrafted donor leukocytes consistently showed over-expression. Conclusions Induction of allograft tolerance involved biological modifications of donor transplants. The increased expression of MHC class I within engrafted donor skins of tolerant mice might be used as the tolerance biomarkers for identifying a state of graft tolerance, and paved the way to advancing our insights into the mechanisms of allo-tolerance induction.

Recipients with in utero induction of tolerance upregulated MHC class I in the engrafted donor skin.

The alterations in MHC class I expression play a crucial step in immune evasion of cancer or virus-infected cells. This study aimed to examine whether tolerized grafts modified MHC class I expression. FVB/N mice were rendered tolerant of C57BL/6 alloantigens by in utero transplantation of C57BL/6 marrows. Postnatally, engrafted donor skins and leukocytes were examined for their MHC expression by quantitative real-time PCR and flow cytometry. Engrafted donor skins upregulated their MHC class I related gene transcripts after short-term (1~2 weeks) or long-term (>1 month) engraftment. This biological phenomenon was simultaneously associated with upregulation of TAP1 gene transcripts, suggesting an important role of TAP1 in the regulation of MHC class I pathway. The surface MHC class I molecules of H-2Kb in engrafted donor leukocytes consistently showed overexpression. Conclusively, the induction of allograft tolerance involved biological modifications of donor transplants. The overexpression of MHC class I within engrafted transplants of tolerant mice might be used as the tolerance biomarkers for identifying a state of graft tolerance.

The MHC Class II transactivator CIITA inhibits Tax-1-mediated HTLV-1 expression and NF-kB activation

Human T-cell Lymphotropic Virus type-1 (HTLV-1) is the causative agent of an aggressive malignancy of CD4+ T lymphocytes. Many evidences have shown that constitutive activation of NF-kB pathway by Tax-1 is crucial for T-cell transformation. We previously demonstrated that CIITA, the master regulator of MHC class II gene transcription, inhibits HTLV-1 replication by blocking the transcription function of the viral transactivator Tax-1. Here we show that CIITA suppresses also Tax-1-mediated activation of the NF-kB pathway. Of note, CIITA interacts with and retains Tax-1 in cytoplasmic fraction and inhibits Tax-1-dependent nuclear translocation of RelA. Moreover, the overexpression of CIITA does not affect Tax-1 interaction with both RelA and IKKg. CIITA acts by suppressing at least the canonical NF-kB pathway, in that it also inhibits activation of NF-kB by Tax-2, which is known to activate NF-kB through the canonical but not the non-canonical pathway. Future studies will be focused to identify the fine mechanisms through which CIITA exerts this inhibitory function. Overall, these findings indicate that CIITA, beside acting as viral restriction factor against HTLV-1 infection, might counteract Tax-1 transforming activity. Thus, assessing the molecular basis of CIITA-mediated Tax-1 inhibition may be important in defining new strategies to control HTLV-1 spreading and oncogenic potential. Supported by: Fondazione Cariplo (2008-2230), AIRC (IG 8862) and Miur PRIN-COFIN 2008. Rawan Abdallah PhD Fellowship is granted by Fondazione Cariplo Bando 2009: Promuovere la formazione di capitale umano di eccellenza: Percorso di eccellenza in tecnologie biomedicali innovative.

Tollip-induced down-regulation of MARCH1

In addition to their classical antigen presenting functions, MHC class II molecules potentiate the TLR-triggered production of pro-inflammatory cytokines. Here, we have addressed the effect of Tollip and MARCH1 on the regulation of MHC II trafficking and TLR signaling. Our results show that MARCH1-deficient mice splenocytes are impaired in their capacity to produce pro-inflammatory cytokines in response to poly(I:C) and that TLR3 and MHC II molecules interact in the endocytic pathway. Knocking down Tollip expression in human CIITA+ HeLa cells increased expression of HLA-DR but reduced the proportion of MHC II molecules associated with the CLIP peptide. Truncation of the HLA-DR cytoplasmic tails abrogated the effect of Tollip on MHC class II expression. While overexpression of Tollip did not affect HLA-DR levels, it antagonized the function of co-transfected MARCH1. We found that Tollip strongly reduced MARCH1 protein levels and that the two molecules appear to compete for binding to MHC II molecules. Altogether, our results demonstrate that Tollip regulates MHC class II trafficking and that MARCH1 may represent a new Tollip target.

Expression of MHC Class I on breast cancer cells correlates inversely with HER2 expression

HER2 is a promising target for immunotherapeutic interventions with T cell-based approaches since it is amplified and overexpressed in 20–30% of breast cancers. However, several previous studies including ours showed that HER2-overexpressing tumors may escape cytotoxic T lymphocyte-mediated lysis by downregulating MHC Class I and components of the antigen-processing machinery. The aims of the present study were to analyze the relationship between HER2 and MHC Class I expression and to elucidate the mechanisms underlying MHC Class I downregulation in breast cancer. We explored expression of HER2, MHC Class I, PTEN, Ki67, estrogen and progesterone expression in 70 breast cancer patients by immunohistochemistry (IHC) and analyzed their correlation. We also explored the components of the signal transduction pathway that are involved in the regulation of MHC Class I expression using small-interfering RNAs targeting HER2 as well as an inhibitor of HER2 signaling. HER2 expression in breast cancers correlated inversely with MHC Class I expression analyzed by IHC. HER2 depletion by small-interfering RNAs resulted in MHC Class I upregulation. Moreover, MHC Class I expression on breast cancer cell lines was upregulated by PD98059, an inhibitor of mitogen-associated protein kinases, in a dose-dependent manner. Thus, agents that target the MAPK signaling pathway may increase MHC Class I expression in breast cancer cells.

The Immunologic Functions of the Neonatal Fc Receptor for IgG

Careful regulation of the body's immunoglobulin G (IgG) and albumin concentrations is necessitated by the importance of their respective functions. As such, the neonatal Fc receptor (FcRn), as a single receptor, is capable of regulating both of these molecules and has become an important focus of investigation. In addition to these essential protection functions, FcRn possesses a number of other functions that are equally as critical and are increasingly coming to attention. During the very first stages of life, FcRn mediates the passive transfer of IgG from mother to offspring both before and after birth. In the adult, FcRn regulates the persistence of both IgG and albumin in the serum as well as the movement of IgG, and any bound cargo, between different compartments of the body via transcytosis across polarized cells. FcRn is also expressed by hematopoietic cells; consistent with this, FcRn regulates MHC class II presentation and MHC class I cross-presentation by dendritic cells. As such, FcRn plays an important role in immune surveillance throughout adult life. The increasing appreciation for FcRn in both homeostatic and pathological conditions is generating an intense interest in the potential for therapeutic modulation of FcRn binding to IgG and albumin.

The tumour suppressor Fhit positively regulates MHC class I expression on cancer cells

MHC class I (MHC-I) molecules are ubiquitously expressed on the cells of an organism. Study of the regulation of these molecules in normal and disease conditions is important. In tumour cells, the expression of MHC-I molecules is very frequently lost, allowing these cells to evade the immune response. Cancers of different histology have shown total loss of MHC-I molecule expression, due to a coordinated transcriptional down-regulation of various antigen-processing machinery (APM) components and/or MHC-I heavy chains. The mechanisms responsible for these alterations remain unclear. We determined the possible genes involved by comparing MHC-I-positive with MHC-I-negative murine metastases derived from the same fibrosarcoma tumour clone. MHC-I-negative metastases showed transcriptional down-regulation of APM and MHC-I heavy chains. The use of microarrays and subtraction cDNA libraries revealed four candidate genes responsible for this alteration, but two of them were ruled out by real-time RT-PCR analyses. The other two genes, AP-2α and Fhit tumour suppressors, were studied by using siRNA to silence their expression in a MHC-I-positive metastatic cell line. AP-2α inhibition did not modify transcriptional expression of APM components or MHC-I heavy chains or surface expression of MHC-I. In contrast, silencing of the Fhit gene produced the transcriptional down-regulation of APM components and MHC-I heavy chains and decreased MHC-I surface expression. Moreover, transfection of Fhit in MHC-I-negative tumour cell lines restored MHC-I cell surface expression. These data indicate that defects in Fhit expression may promote MHC-I down-regulation in cancer cells and allow escape from immunosurveillance(#).

NLRC5 regulates MHC class I antigen presentation in host defense against intracellular pathogens

NOD-like receptors (NLRs) are a family of intracellular proteins that play critical roles in innate immunity against microbial infection. NLRC5, the largest member of the NLR family, has recently attracted much attention. However, in vitro studies have reported inconsistent results about the roles of NLRC5 in host defense and in regulating immune signaling pathways. The in vivo function of NLRC5 remains unknown. Here, we report that NLRC5 is a critical regulator of host defense against intracellular pathogens in vivo. NLRC5 was specifically required for the expression of genes involved in MHC class I antigen presentation. NLRC5-deficient mice showed a profound defect in the expression of MHC class I genes and a concomitant failure to activate L. monocytogenes-specific CD8(+) T cell responses, including activation, proliferation and cytotoxicity, and the mutant mice were more susceptible to the pathogen infection. NLRP3-mediated inflammasome activation was also partially impaired in NLRC5-deficient mice. However, NLRC5 was dispensable for pathogen-induced expression of NF-κB-dependent pro-inflammatory genes as well as type I interferon genes. Thus, NLRC5 critically regulates MHC class I antigen presentation to control intracellular pathogen infection.

The MHC-II transactivator CIITA, a viral restriction factor inhibiting the replication of Human T-Cell Lymphotropic Virus Type 1

Human T-cell Lymphotropic Virus type-1 (HTLV-1) is the causative agent of an aggressive malignancy of CD4+ T lymphocytes. It is believed that the viral transactivator Tax-1 is a major player in T-cell transformation. Thus, targeting Tax-1 protein is regarded as a possible strategy to arrest viral replication and ultimately to counteract neoplastic transformation. Here, we demonstrated that CIITA, the master regulator of MHC class II gene transcription, inhibits HTLV-1 replication by blocking the transactivating function of Tax-1. Co-immunoprecipitation experiments have shown that CIITA and Tax-1 physically interact in vivo and that the first 108 amino acids of Tax-1 were necessary for this binding. Two adjacent regions (1-252 and 253-410) of CIITA bound independently to Tax-1, but only region 1-252 mediated Tax-1 inhibition, in agreement with the fact that CIITA residues from positions 64-124 were required to block Tax-1 transactivation. CIITA inhibitory action on Tax-1 function correlated with the nuclear localization of CIITA and was independent of the transcription factor NF-YB, previously involved in CIITA-mediated inhibition of Tax-2 of HTLV-2, a virus with still elusive pathogenic action. Furthermore, CIITA severely impaired the physical and functional interaction of Tax-1 with the cellular co-activator PCAF, which is required for the optimal activation of HTLV-1 promoter. Accordingly, the over-expression of PCAF restored Tax-1-dependent transactivation of the viral LTR promoter inhibited by CIITA. These findings strongly support our original observation that CIITA, beside increasing the antigen-presenting function for pathogen antigens, acts as an endogenous restriction factor against human retroviruses by blocking virus replication and spreading.

Three novel downstream promoter elements regulate MHC class I promoter activity in mammalian cells.

BackgroundMHC class I transcription is regulated by two distinct types of regulatory pathways: 1) tissue-specific pathways that establish constitutive levels of expression within a given tissue and 2) dynamically modulated pathways that increase or decrease expression within that tissue in response to hormonal or cytokine mediated stimuli. These sets of pathways target distinct upstream regulatory elements, have distinct basal transcription factor requirements, and utilize discrete sets of transcription start sites within an extended core promoter.Methodology/Principal FindingsWe studied regulatory elements within the MHC class I promoter by cellular transfection and in vitro transcription assays in HeLa, HeLa/CIITA, and tsBN462 of various promoter constructs. We have identified three novel MHC class I regulatory elements (GLE, DPE-L1 and DPE-L2), located downstream of the major transcription start sites, that contribute to the regulation of both constitutive and activated MHC class I expression. These elements located at the 3′ end of the core promoter preferentially regulate the multiple transcription start sites clustered at the 5′ end of the core promoter.Conclusions/SignificanceThree novel downstream elements (GLE, DPE-L1, DPE-L2), located between +1 and +32 bp, regulate both constitutive and activated MHC class I gene expression by selectively increasing usage of transcription start sites clustered at the 5′ end of the core promoter upstream of +1 bp. Results indicate that the downstream elements preferentially regulate TAF1-dependent, relative to TAF1-independent, transcription.

Ubiquitination regulates MHC class II-peptide complex retention and degradation in dendritic cells

The expression and turnover of MHC class II-peptide complexes (pMHC-II) on the surface of dendritic cells (DCs) is essential for their ability to activate CD4 T cells efficiently. The half-life of surface pMHC-II is significantly greater in activated (mature) DCs than in resting (immature) DCs, but the molecular mechanism leading to this difference remains unknown. We now show that ubiquitination of pMHC-II by the E3 ubiquitin ligase membrane-associated RING-CH 1 (March-I) regulates surface expression, intracellular distribution, and survival of pMHC-II in DCs. DCs isolated from March-I-KO mice express very high levels of pMHC-II on the plasma membrane even before DC activation. Although ubiquitination does not affect the kinetics of pMHC-II endocytosis from the surface of DCs, the survival of pMHC-II is enhanced in DCs obtained from March-I-deficient and MHC-II ubiquitination-mutant mice. Using pMHC-II-specific mAb, we show that immature DCs generate large amounts of pMHC-II that are remarkably stable under conditions in which pMHC-II ubiquitination is blocked. Thus, the cellular distribution and stability of surface pMHC-II in DCs is regulated by ubiquitin-dependent degradation of internalized pMHC-II.

ITAM signaling in dendritic cells controls T helper cell priming by regulating MHC class II recycling

AbstractImmature dendritic cells (DCs) specialize in antigen capture and maintain a highly dynamic pool of intracellular major histocompatibility complex class II (MHCII) that continuously recycles from peptide loading compartments to the plasma membrane and back again. This process facilitates sampling of environmental antigens for presentation to T helper cells. Here, we show that a signaling pathway mediated by the DC immunoreceptor tyrosine-based activation motif (ITAM)–containing adaptors (DAP12 and FcRγ) and Vav family guanine nucleotide exchange factors controls the half-life of surface peptide-MHCII (pMHCII) complexes and is critical for CD4 T-cell triggering in vitro. Strikingly, mice with disrupted DC ITAMs show defective T helper cell priming in vivo and are protected from experimental autoimmune encephalitis. Mechanistically, we show that deficiency in ITAM signaling results in increased pMHCII internalization, impaired recycling, and an accumulation of ubiquitinated MHCII species that are prematurely degraded in lysosomes. We propose a novel mechanism for control of T helper cell priming.

Lack of association of the CIITA-168A→G promoter SNP with myasthenia gravis and its role in autoimmunity

BackgroundThe major histocompatibility complex class II transactivator (CIITA) regulates MHC class II gene expression. A promoter SNP -168A→G (rs3087456) has previously been shown to be associated with susceptibility to several immune mediated disorders, including rheumatoid arthritis (RA), multiple sclerosis (MS) and myocardial infarction (MI). Myasthenia gravis (MG) is an autoimmune disorder which has previously been shown to be associated with polymorphisms of several autoimmune predisposing genes, including IL-1, PTPN22, TNF-α and the MHC. In order to determine if allelic variants of rs3087456 increase predisposition to MG, we analyzed this SNP in our Swedish cohort of 446 MG patients and 1866 controls.ResultsNo significant association of the SNP with MG was detected, neither in the patient group as a whole, nor in any clinical subgroup. The vast majority of previous replication studies have also not found an association of the SNP with autoimmune disorders.ConclusionsWe thus conclude that previous findings with regard to the role of the CIITA -168A→G SNP in autoimmunity may have to be reconsidered.

PU.1 Binds to a Distal Regulatory Element That Is Necessary for B Cell-Specific Expression of CIITA

The transcriptional coactivator CIITA regulates MHC class II genes. In the mouse, CIITA is expressed from three distinct promoters (pI, pIII, and pIV) in a developmental and cell type-specific manner with pIII being responsible for B lymphocyte-specific expression. Although the promoter proximal sequences that regulate CIITA in B cells have been described, nothing is known about additional distal elements that may regulate its expression in B cells. Sequence homology comparisons, DNase I hypersensitivity assays, and histone modification analysis revealed a potential regulatory element located 11 kb upstream of pIII. Deletion of this element, termed hypersensitive site 1 (HSS1), in a bacterial artificial chromosome encoding the entire CIITA locus and surrounding genes, resulted in a complete loss of CIITA expression from the bacterial artificial chromosome following transfection into B cells. HSS1 and pIII displayed open chromatin architecture features in B cell but not in plasma cell lines, which are silenced for CIITA expression. PU.1 was found to bind HSS1 and pIII in B cells but not in plasma cells. Depletion of PU.1 by short hairpin RNA reduced CIITA expression. Chromatin conformation capture assays showed that HSS1 interacted directly with pIII in B cells and that PU.1 was important for this interaction. These results provide evidence that HSS1 is required for B cell-specific expression of CIITA and that HSS1 functions by interacting with pIII, forming a long-distance chromatin loop that is partly mediated through PU.1.

Correction: NF-κB, and not MYCN, Regulates MHC Class I and Endoplasmic Reticulum Aminopeptidases in Human Neuroblastoma Cells

Correction: NF-κB, and not MYCN, Regulates MHC Class I and Endoplasmic Reticulum Aminopeptidases in Human Neuroblastoma Cells