Hereditary major histocompatibility complex (MHC) class II deficiency (or bare lymphocyte syndrome) is a form of severe primary immunodeficiency with a total lack of MHC class II expression. It is due to a defect in the regulation of MHC class II genes. A novel gene was isolated by complementation c …

Major histocompatibility (MHC) class II molecules are transmembrane proteins that have a central role in development and control of the immune system. The protein encoded by this gene, along with regulatory factor X-associated protein and regulatory factor-5, forms a complex that binds to the X box motif of certain MHC class II gene promoters and activates their transcription. Once bound to the promoter, this complex associates with the non-DNA-binding factor MHC class II transactivator, which controls the cell type specificity and inducibility of MHC class II gene expression. This protein contains ankyrin repeats involved in protein-protein interactions. Mutations in this gene have been linked to bare lymphocyte syndrome type II, complementation group B. Two transcript variants encoding different isoforms have been described for this gene, with only one isoform showing activation activity.[7]. ...

The current model predicts that several chromatin organizational states may exist: inactive, poised, and active. As depicted, the active state may occur in MHC-II constitutively expressing B lymphocytes and cells induced to express MHC-II genes by IFN-γ. The active state would feature interactions between XL9 and the promoter regions of the HLA-DRB1 and HLA-DQA1 genes. The data collected using the 3C assay represent a population view and not individual haplotypes or alleles. Thus, with a recent report suggesting that active genes do not continuously transcribe their DNA (40), it was possible that only one of the two flanking genes was transcribed at a time or interacting with XL9. However, the RNA FISH data argue that all combinations of expression occur, with the predominant combination including HLA-DRB1 and HLA-DQA1 expression from the same chromosome. The observation of a CIITA-dependent 3C product between the promoter regions of HLA-DRB1 and HLA-DQA1 suggests that both promoter regions are ...

Authors: Dearborn DC, Gager AB, McArthur AG, Gilmour ME, Mandzhukova E, Mauck RA.. Mol Ecol. 2016 Sep;25(17):4355-67.. Genes of the major histocompatibility complex (MHC) exhibit heterozygote advantage in immune defence, which in turn can select for MHC-disassortative mate choice. However, many species lack this expected pattern of MHC-disassortative mating. A possible explanation lies in evolutionary processes following gene duplication: if two duplicated MHC genes become functionally diverged from each other, offspring will inherit diverse multilocus genotypes even under random mating. We used locus-specific primers for high-throughput sequencing of two expressed MHC Class II B genes in Leachs storm-petrels, Oceanodroma leucorhoa, and found that exon 2 alleles fall into two gene-specific monophyletic clades. We tested for disassortative vs. random mating at these two functionally diverged Class II B genes, using multiple metrics and different subsets of exon 2 sequence data. With good ...

摘 要：II类反式激活因子(class II trans-activator， CIITA)为非DNA结合蛋白，在MHC II类基因的转录激活过程中以协同激活分子的形式发挥主导开关的作用。CIITA还可以调节其他与抗原递呈相关的基因，如H-2M基因、Ia相关恒定链(Ii chain)基因等。结构上，CIITA分子又是NOD样受体(NOD-like receptor， NLR)家族成员之一，其功能与固有免疫密切相关。除此之外，CIITA在T细胞分化、FasL介导的细胞死亡、胶原的合成等方面也发挥着重要的调节作用 ...

MHC‐II deficiency is a genetic disease of gene regulation. It is due to defects in regulatory factors that are essential for both constitutive and IFN‐γ inducible expression of MHC‐II genes (Reith et al., 1995, 1997; Mach et al., 1996). Together with a number of in vitro generated regulatory mutants, MHC‐II deficiency patients have been classified into at least four different complementation groups (A, B, C and D) believed to correspond to at least four distinct regulatory genes (Hume and Lee, 1989; Benichou and Strominger, 1991; Seidl et al., 1992; Lisowska‐Grospierre et al., 1994). The disease thus provides a genetic approach to identify genes encoding several of the trans‐acting regulatory factors involved and therefore represents an ideal model system for the dissection of the molecular mechanisms controlling transcriptional activation of MHC‐II genes. The relevant regulatory genes can be identified on the basis of a powerful functional criterion, namely the ability to ...

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OBJECTIVE To investigate the cloning and biological activities of riboenzymes against major histocompatibility complex (MHC) class II transactivator (CIITA) so as to explore the feasibility of using hammerhead riboenzyme to create immune tolerance. METHODS Three riboenzymes against MHC CIITA were synthesized and their activities were evaluated in vitro. Rz464, the riboenzyme with a better digestion effect, was inserted into the vector pIRES2-EGFP (then called pRz464). Human B lymphoma cells of Daudi line were cultured and transfected with pRz464 (then called pRz464-D). Cultured Daudi cells transfected with riboenzyme without the ability against CIITA (Rz-D) were used as control group. The expressions of classic MHC CIITA (HLA-DR, DP, and DQ) on the surface of Daudi cells before and after transfection were examined by flow cytometry. RESULTS The expressions of HLA-DR, DP, and DQ on the surface of cultured Daudi cells (Rz-D) were 97.9 +/- 0.8%, 94.3 +/- 1.1%, and 54.4 +/- 3.1% respectively. The

Predicted to have activating transcription factor binding activity; protein C-terminus binding activity; and transcription regulatory region DNA binding activity. Involved in negative regulation of transcription, DNA-templated and response to interferon-gamma. Predicted to localize to the PML body; cell surface; and cytosol. Used to study MHC class II deficiency and osteoporosis. Human ortholog(s) of this gene implicated in Addisons disease; MHC class II deficiency; autoimmune hypersensitivity disease (multiple); myocardial infarction; and rheumatoid arthritis (multiple). Is expressed in bladder; central nervous system; and retina. Orthologous to human CIITA (class II major histocompatibility complex transactivator ...

The use of genetic mutants has been invaluable in discovering components of molecular pathways. One of the most successful examples is the elucidation of intracellular mediators and signal transducers, which contribute to an IFN response. For example, the tyk kinase, which is associated with the receptor for type I IFN, was first discovered with the use of a gene complementation approach made possible by the availability of mutant cell lines defective in their responses to type I IFN (46). Similarly, a number of mutant cell lines defective in either type I or II IFN signaling have been instrumental in confirming the functional roles of Janus kinases and STAT molecules in the IFN pathway (47, 48).. Along the same vein, four mutant cell lines, G1 to G4, were genetically chosen on the basis of their selective loss of IFN-γ-induced MHC class II expression while retaining expression of other IFN-γ-induced genes (1). Analyses of these and other mutant lines clearly indicate that the IFN-γ induction ...

J Immunol. 2001 Oct 1;167(7):3626-34. Harton JA, Zika E, Ting JP. The histone acetyltransferase domains of CREB-binding protein (CBP) and p300/CBP-associated factor are not necessary for cooperativity with the class II transactivator. J Biol Chem. 2001 Oct 19;276(42):38715-20. Deffrennes V, Vedrenne J, Stolzenberg MC, Piskurich J, Barbieri G, Ting JP, Charron D, Alcaide-Loridan C. Constitutive expression of MHC class II genes in melanoma cell lines results from the transcription of class II transactivator abnormally initiated from its B cell-specific promoter. J Immunol. 2001 Jul 1;167(1):98-106. Li G, Harton JA, Zhu X, Ting JP. Downregulation of CIITA function by protein kinase a (PKA)-mediated phosphorylation: mechanism of prostaglandin E, cyclic AMP, and PKA inhibition of class II major histocompatibility complex expression in monocytic lines. Mol Cell Biol. 2001 Jul;21(14):4626-35. Linhoff MW, Harton JA, Cressman DE, Martin BK, Ting JP. Two distinct domains within CIITA mediate ...

Cited by the Following Articles in PubMed: Dagan A. Loisel, Matthew V. Rockman, Gregory A. Wray, Jeanne Altmann, and Susan C. Alberts. Ancient polymorphism and functional variation in the primate MHC-DQA1 5′ cis-regulatory region. Proc Natl Acad Sci U S A. 2006 October 31; 103(44): 16331-16336. Published online 2006 October 19. doi: 10.1073/pnas.0607662103. Dissection of the role of MHC class II A and E genes in autoimmune susceptibility in murine lupus models with intragenic recombination Danqing Zhang, Keishi Fujio, Yi Jiang, Jingyuan Zhao, Norihiro Tada, Katsuko Sudo, Hiromichi Tsurui, Kazuhiro Nakamura, Kazuhiko Yamamoto, Hiroyuki Nishimura, Toshikazu Shira, and Sachiko Hirose. Proc Natl Acad Sci U S A. 2004 September 21; 101(38): 13838-13843. Published online 2004 September 10. doi: 10.1073/pnas.0405807101. J V Taylor, L E Gordon, and H C Polk, Jr. Early decrease in surface expression of HLA-DQ predicts the development of infection in trauma patients. Clin Exp Immunol. 2000 December; ...

The MHC class II gene Aa was disrupted by targeted mutation in embryonic stem (ES) cells derived from C57BL/6 mice to prevent expression of MHC class II molecules. Contrary to previous reports, the effect of the null-mutation on T cell development was investigated in C57BL/6 mice, which provide a defined genetic background. The complete lack of cell surface expression of MHC class II molecules in B6-Aa0/Aa0 homozygous mutant mice was directly demonstrated by cytofluorometric analysis using anti-Ab and anti-Ia specific mAbs. Development of CD4+CD8- T cells in the thymus was largely absent except for a small population of thymocytes expressing high levels of CD4 together with low amounts of CD8. The majority of these cells express the TCR at high density. Although mature CD4+CD8- T cells were undetectable in the thymus, some T cells with a CD4+CD8-TCRhigh phenotype were found in lymph nodes and spleen. Peripheral T cells from the mutant mice can be polyclonally activated in vitro with the mitogen ...

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The human adaptive immune response is regulated by major histocompatibility complex class II (MHCII) molecules. Initiation of the immune response against infection is directly related to the level of expression of MHCII molecules in the cell. A multi-protein complex, termed the MHCII enhanceosome, is responsible for the expression of MHCII genes. The key DNA binding component of the MHCII enhanceosome is the RFX complex. The RFX complex is comprised of three proteins - RFX5, RFXAP, and RFXB - all of which are required for DNA binding and assembly of the enhanceosome. Mutations or deletions in any of the RFX proteins that prevent RFX assembly or the recruitment of other proteins in the MHCII enhanceosome, results in a severe immunodeficiency disorder. RFX5 is comprised of four domains: the oligomerization domain, the RFX DNA binding domain, the dimerization domain, and the transactivation domain. RFX5 dimerizes through both the oligomerization domain and the dimerization domain, and this ...

Class II transactivator (CIITA) is a global transcriptional coactivator of human leukocyte antigen-D (HLA-D) genes. CIITA contains motifs similar to guanosine triphosphate (GTP)-binding proteins. This report shows that CIITA binds GTP, and mutations in these motifs decrease its GTP-binding and transactivation activity. Substitution of these motifs with analogous sequences from Ras restores CIITA function. CIITA exhibits little GTPase activity, yet mutations in CIITA that confer GTPase activity reduce transcriptional activity. GTP binding by CIITA correlates with nuclear import. Thus, unlike other GTP-binding proteins, CIITA is involved in transcriptional activation that uses GTP binding to facilitate its own nuclear import. ...

Functions as a transcription factor during endoplasmic reticulum (ER) stress by regulating the unfolded protein response (UPR). Required for cardiac myogenesis and hepatogenesis during embryonic development, and the development of secretory tissues such as exocrine pancreas and salivary gland. Involved in terminal differentiation of B lymphocytes to plasma cells and production of immunoglobulins. Modulates the cellular response to ER stress in a PIK3R-dependent manner. Binds to the cis-acting X box present in the promoter regions of major histocompatibility complex class II genes. Involved in VEGF-induced endothelial cell (EC) proliferation and retinal blood vessel formation during embryonic development but also for angiogenesis in adult tissues under ischemic conditions. Functions also as a major regulator of the UPR in obesity-induced insulin resistance and type 2 diabetes for the management of obesity and diabetes prevention.

Complete information for CIITA gene (Protein Coding), Class II Major Histocompatibility Complex Transactivator, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium

MHC Class II I-Ab, eFluor 450, clone: AF6-120.1, eBioscience™ 25μg; eFluor 450 MHC Class II I-Ab, eFluor 450, clone: AF6-120.1, eBioscience™ Primary...

MHC Class II I-Ab Mouse anti-Mouse, PE, Clone: AF6-120.1, eBioscience™ 100μg; PE MHC Class II I-Ab Mouse anti-Mouse, PE, Clone: AF6-120.1, eBioscience™...

As summarized in Section 1, EAT susceptibility and resistance are categorized by their MHC class II gene differences. Since susceptible mice have naturally existing CD4+CD25+ T cells (Morris and Kong, 2004), it was of interest to determine if CD4+CD25+ T cells also influence EAT induction in resistant strains. In pilot experiments using two EAT-resistant strains, prior depletion of CD4+CD25+ T cells in both BALB c (H2d) mice (Wei et al, 2004) and B10 (H2b) mice (Morris et al., 2004) enabled the.... ...

In contrast to the mammalian major histocompatibility complex (MHC), where the MHC class I and class II loci reside in close vicinity to one another, the bony fishes have unlinked MHC class I and class II. Previous studies ...

Abstract. Abstract 2333The gene locus BX648577 (FLJ27352/hypothetical LOC145788) was recently identified as part of a gene fusion with Class II Transactivator (

Background: The vulnerability to a severe viral infection reported to be associated with genetic variants in immune response genes using case reports and studies GWAS. SARS-CoV-2 is a viral disease that appears that caused millions of COVID 19 cases worldwide. Read more…. ...

Cases reported • Severe Combined Immunodeficiency; Immunodeficiency, Severe Combined; Omenn Syndrome; Bare Lymphocyte Syndrome. On-line free medical diagnosis assistant. Ranked list of possible diseases from either several symptoms or a full patient history. A similarity measure between symptoms and diseases is provided.

TY - JOUR. T1 - IN-UTERO TRANSPLANTATION OF STEM CELLS IN BARE LYMPHOCYTE SYNDROME. AU - Touraine, J. L.. AU - Raudrant, D.. AU - Royo, C.. AU - Rebaud, A.. AU - Roncarolo, M. G.. AU - Souillet, G.. AU - Philippe, N.. AU - Touraine, F.. AU - Bétuel, H.. PY - 1989/6/17. Y1 - 1989/6/17. UR - http://www.scopus.com/inward/record.url?scp=0024400712&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0024400712&partnerID=8YFLogxK. U2 - 10.1016/S0140-6736(89)92819-5. DO - 10.1016/S0140-6736(89)92819-5. M3 - Article. C2 - 2567387. AN - SCOPUS:0024400712. VL - 333. SP - 1382. JO - The Lancet. JF - The Lancet. SN - 0140-6736. IS - 8651. ER - ...

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TY - JOUR. T1 - MHC class II transactivator represses human IL-4 gene transcription by interruption of promoter binding with CBP/p300, STAT6 and NFAT1 via histone hypoacetylation. AU - Zhou, Xiaorong. AU - Jiang, Yang. AU - Lu, Liming. AU - Ding, Qing. AU - Jiao, Zhijun. AU - Zhou, Yun. AU - Xin, Lijun. AU - Chou, Kuang Yen. N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2007/12. Y1 - 2007/12. N2 - In addition to its property of enhancing major histocompatibility complex (MHC) class II expression, the class II transactivator (CIITA) was recently demonstrated to be involved in T helper type 1/type 2 (Th1/Th2) differentiation by regulating interleukin-4 (IL-4) gene transcription. There was however, controversy regarding whether CIITA promotes or suppresses IL-4 expression in the experiments with transgenic mice. To clarify the discrepancy by using simpler experimental systems, human Jurkat T cells that express IL-4 but not interferon-γ, even if stimulated with phorbol ...

Mutations in human and/or mouse homologs are associated with this disease. Synonyms: bare lymphocyte syndrome type II; BLSII; SCID due to absent class II HLA antigens (disorder)

BACKGROUND: Multiple sclerosis (MS) is a complex trait in which alleles at or near the class II loci HLA-DRB1 and HLA-DQB1 contribute significantly to genetic risk. The MHC class II transactivator (MHC2TA) is the master controller of expression of class II genes, and methylation of the promoter of this gene has been previously been shown to alter its function. In this study we sought to assess whether or not methylation of the MHC2TA promoter pIV could contribute to MS disease aetiology. METHODS: In DNA from peripheral blood mononuclear cells from a sample of 50 monozygotic disease discordant MS twins the MHC2TA promoter IV was sequenced and analysed by methylation specific PCR. RESULTS: No methylation or sequence variation of the MHC2TA promoter pIV was found. CONCLUSION: The results of this study cannot support the notion that methylation of the pIV promoter of MHC2TA contributes to MS disease risk, although tissue and timing specific epigenetic modifications cannot be ruled out.

Eike, Morten Christoph; Skinningsrud, Beate; Kvien, Tore Kristian; Stormyr, Alice; Undlien, Dag Erik & Lie, Benedicte Alexandra (2010). Support for involvement of CIITA gene variants in rheumatoid arthritis. Show summary The class II major histocompatibility complex (MHC) transactivator (CIITA) is a crucial regulator of MHC class II gene expression. Due to the established role of MHC class II in autoimmunity, CIITA is therefore an excellent candidate for involvement in autoimmune diseases. Accordingly, the rs3087456 A,G promoter SNP in this gene has been reported associated with rheumatoid arthritis (RA) and the intronic rs8048002 T,C SNP with autoimmune Addisons disease (AAD). In this study, we genotyped 819 Norwegian RA patients and 2152 controls for both of these SNPs. Results: The rs3087456 GG genotype was significantly associated with RA in a recessive model, both in our material (OR 1.50 [95% CI 1.10-2.05], P=0.0093) and in an updated meta-analysis of 15 cohorts, totalling 13154 RA ...

The RV144 vaccine produced two Env-specific antibody responses that correlated with HIV-1 acquisition (3). Because HLA class II molecules are important in the initiation of antibody responses, we hypothesized that variation in HLA class II genes might influence response to the vaccine. DRB1, DQB1, and DPB1 loci were typed in the RV144 vaccine recipients, and the alleles found were tested for an effect on magnitude of vaccine-induced responses and for interactions with the two vaccine-elicited immune responses that significantly affected HIV-1 acquisition. Both Env-specific antibody responses previously identified were found to correlate with HIV-1 acquisition only in the presence of specific HLA class II alleles.. Haynes et al. (3) observed that high levels of IgA antibody binding to Env correlated with reduced vaccine efficacy that was not distinguishable from the placebos in RV144. Here, we report that it is only in the presence of a single allele, DQB1*06, that high levels of Env-specific IgA ...

Sequence variation at a major histocompatibility complex (MHC) class II gene was examined in Hypogeomys antimena, a monogamous endemic rodent of Madagascar. The study was conducted throughout its remaining geographical range (20 × 40 km) by direct sequencing and single-strand conformation polymorphism (SSCP). The objectives of the study were: (i) to investigate levels of polymorphism in the MHC complex of a highly endangered species that experienced a severe reduction in population size; and (ii) to investigate the genetic mating system by assessing the frequency of extra-pair paternity (EPP) as EPP might have important consequences to increase gene flow and, therefore, genetic variability within a population. The amplified gene segment had a very low variability (only two alleles) in H. antimena compared with other mammalian species. The alleles segregated consistently with Mendelian expectations in families. No case of EPP was found. The present data suggest no difference between the social ...

We used a hit and run gene targeting strategy to generate mice expressing only the p31 isoform of the conserved invariant (Ii) chain associated with major histocompatibility complex (MHC) class II molecules. Spleen cells from these mice appear indistinguishable from wild type with respect to class II subunit assembly, transport, peptide acquisition, surface expression, and the ability to present intact protein antigens. Moreover, these mutant mice have normal numbers of thymic and peripheral CD4+ T cells, and intact CD4+ T-dependent proliferative responses towards a soluble antigen. In short, MHC class II expression and function are surprisingly unaffected in mice lacking p41 invariant chain, implying that the p31 and p41 isoforms may be functionally redundant in the intact animal.

A macrophage activator, IL-4 stimulates phagocytic activity and MHC class II gene expression. IL-4 stimulates isotype switching by activating the promoters for Iε, and Iγ1 (the I regions for ε and γ1 heavy chain constant region genes). IL-4 is pivotal in regulating the IgE response: IgG1 and IgE account ∼2% of all antibodies secreted by splenic B cells incubated with LPS; IgG1 accounts for ∼50% and IgE accounts for ∼20% of all antibodies secreted by B cells incubated with LPS and IL-4. IL-4 knockout mice cannot mount an IgE response to parasites. Also, CD4 T cells activated in presence of IL-4 develop into TH2 cells (especially if IL-6 is also present); IL-4 and IL-10 both inhibit T cell differentiation into TH1 cells ...

Despite the stringent requirements of class II genes to have both a sharp increase and decrease in transcript levels, 792 fly genes were classified in this class. This is consistent with earlier reports in D. melanogaster (Arbeitman et al, 2002) and also C. elegans (Baugh et al, 2003). As shown in Table Ib, the class II genes are enriched in transcription factors and lethal phenotype genes (hereafter referred to as lethals; see Materials and methods) and not surprisingly, this class shows an overrepresentation of genes with functions involved in development. More specifically, many of these genes are annotated as encoding proteins involved in histogenesis, organogenesis, ectoderm development, cell differentiation, and cell fate commitment (Table Ib; GO analysis). The class II group is also enriched in genes that encode well‐characterized transcription factors (P,0.05, t2‐test).. Of the class II genes, 303 (38%) are found in only three groups; a, b, and c, each defined by specific ...

The first step in the induction of immune responses, whether humoral or cell mediated, requires the interaction between antigen-presenting cells and T lymphocytes restricted at the major histocompatibility complex (MHC). These cells invariably express MHC class II molecules (HLA-D region in man and Ia in mouse) which are recognized by T cells of the helper/inducer subset in association with antigen fragments. Interestingly, in certain pathological conditions, for example in autoimmune diseases such as thyroiditis and diabetic insulitis, class II molecules may be expressed on epithelial cells that normally do not express them. We speculated that these cells may be able to present their surface autoantigens to T cells, and that this process may be crucial to the induction and maintenance of autoimmunity. A critical test of this hypothesis would be to determine whether epithelial cells bearing MHC class II molecules (class II+ cells) can present antigen to T cells. We report here that class II+ thyroid

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Several mutants derived from transformed human B cell lines are defective in expressing major histocompatibility complex (MHC) class II genes. The failure to express a class II gene in at least one such mutant line has been mapped to the MHC class II X box, a conserved transcriptional element in the promoter region. A complementary DNA encoding a DNA-binding protein (human X box binding protein, hXBP-1) whose target is the human DR alpha X box and the 3 flanking region has now been cloned. This complementary DNA encoded a protein with structural similarities to the c-jun proto-oncogene product, and its target sequence was closely related to the palindromic target sequence of c-jun. Mutation of the hXBP-1 DNA target sequence decreased DR alpha promoter activity in vivo. These studies suggest that the hXBP-1 protein acts as a transcription factor in B cells. ...

Clone REAL362 is an antibody fragment derived from the full MHC Class II (I-Ab) antibody molecule. It displays no binding to Fc receptors. The recombinantly engineered antibody fragments are multimerized to form the REAlease Complex to bind markers with high avidity.Clone REAL362 recognizes the mouse MHC class II alloantigen I-Ab of H-2b bearing mouse strains. It also cross-reacts with the H-2k and H-2u haplotypes, but reactivity to other haplotypes like, for example, d, f, g7, p, q, r, and s has not been observed. MHC class II is expressed on antigen-presenting cells, such as dendritic cells, monocytes, macrophages, B cells in lymphoid and non-lymphoid tissue, thymic epithelial cells, and on subsets of hematopoietic progenitor cells in the bone marrow.The REAlease Kits consist of the respective fluorochrome-conjugated REAlease Complexes and the REAlease Support Kit for removal of the REAlease Complexes and optional relabeling with different fluorochrome-conjugated REAlease Complexes. - Österreich

The proteasome is a 700-kD multisubunit enzyme complex with several proteolytically active sites. The enzyme complex is involved in both ubiquitin-dependent and -independent protein degradation and may contribute to the processing of antigens presented by major histocompatibility complex (MHC) class I molecules. Here we demonstrate that treatment of mouse fibroblast cells with 20 U interferon gamma (IFN-gamma) for 3 d induces a change in the proteasome subunit composition and that the beta-type subunit LMP2, which is encoded in the MHC class II region, is incorporated into the enzyme complex. This is paralleled by reduction of the homologous delta-subunit. IFN-gamma stimulation results in a downregulation of the chymotrypsin-like Suc-LLVY-MCA peptide hydrolyzing activity of 20S proteasomes whereas the trypsin-like activity remains unaffected. When tested as a substrate a synthetic 25-mer polypeptide whose sequence covers the antigenic nonapeptide YPHFMPTNL of the MCMV pp89, 20S proteasomes of ...

The structural basis of the interaction between the CD4 coreceptor and a class II major histocompatibility complex (MHC) is described. The crystal structure of a complex containing the human CD4 N-terminal two-domain fragment and the murine I-A(k) class II MHC molecule with associated peptide (pMHCII) shows that only the top corner of the CD4 molecule directly contacts pMHCII. The CD4 Phe-43 side chain extends into a hydrophobic concavity formed by MHC residues from both alpha2 and beta2 domains. A ternary model of the CD4-pMHCII-T-cell receptor (TCR) reveals that the complex appears V-shaped with the membrane-proximal pMHCII at the apex. This configuration excludes a direct TCR-CD4 interaction and suggests how TCR and CD4 signaling is coordinated around the antigenic pMHCII complex. Human CD4 binds to HIV gp120 in a manner strikingly similar to the way in which CD4 interacts with pMHCII. Additional contacts between gp120 and CD4 give the CD4-gp120 complex a greater affinity. Thus, ligation of ...

Single-nucleotide polymorphisms (SNPs) in the major histocompatibility complex class II transactivator (MHC2TA) gene encoding the class II transactivator have been associated with multiple sclerosis, rheumatoid arthritis, and myocardial infarction in the Swedish population. We used a case-control approach to investigate the prevalence of a relevant variant in Swedish systemic lupus erythematosus (SLE) cohorts to determine whether SLE shares the same MHC2TA susceptibility allele as the other diseases. No differences were observed between cases and control subjects at either the allele or genotype levels. Furthermore, no significant correlations were found when comparing different clinical and serological SLE phenotypes. This particular polymorphism rs3087456 of the MHC2TA gene does not appear to influence genetic susceptibility to SLE in the Swedish population. We conclude that our data support neither allelic nor genotype association between the MHC2TA SNP and SLE.. ...

To investigate the relationship between meiotic crossover hot spots and block-like linkage disequilibrium (LD), we have extended our high-resolution studies of the human MHC class II region to a 90-kb segment upstream of the HLA-DOA gene. LD blocks in this region are not as well defined as in the neighboring 210-kb DNA segment but do show two regions of LD breakdown in which coalescent analysis indicates substantial historical recombination. Sperm crossover analysis of one region revealed a novel localized hot spot similar in intensity and morphology to most other MHC hot spots. Crossovers at this hot spot are not obviously affected by a large insertion/deletion polymorphism near the hot spot. The second region of LD breakdown, within the DPB1 gene, shows an extremely low level of sperm crossover activity and does not contain a sperm crossover hot spot. These results highlight the complexity of LD patterns and the importance of experimentally verifying crossover hot spots ...

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PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Somatic mutations in CREBBP occur frequently in B-cell lymphoma. Here, we show that loss of CREBBP facilitates the development of germinal center (GC)-derived lymphomas in mice. In both human and murine lymphomas, CREBBP loss-of-function resulted in focal depletion of enhancer H3K27 acetylation and aberrant transcriptional silencing of genes that regulate B-cell signaling and immune responses, including class II MHC. Mechanistically, CREBBP-regulated enhancers are counter-regulated by the BCL6 transcriptional repressor in a complex with SMRT and HDAC3, which we found to bind extensively to MHC class II loci. HDAC3 loss-of-function rescued repression of these enhancers and corresponding genes, including MHC class II, and more profoundly suppressed CREBBP-mutant lymphomas in vitro and in vivo. Hence, CREBBP loss-of-function contributes to lymphomagenesis by enabling unopposed suppression of enhancers by BCL6/SMRT/HDAC3 complexes, suggesting HDAC3-targeted therapy as a precision approach for ...

The Genetics Society of America (GSA), founded in 1931, is the professional membership organization for scientific researchers and educators in the field of genetics. Our members work to advance knowledge in the basic mechanisms of inheritance, from the molecular to the population level.. Online ISSN: 1943-2631. ...

The ability of various B10 congenic resistant strains to respond to the alloantigen H-2.2 was tested. High and low antibody-producing strains were distinguished by their anti-H-2.2 hemagglutinating respones. However, these strains do not differ in their ability to respond to these antigenic differences in the mixed lymphocyte culture. The humoral response to the H-2.2 alloantigen was shown to be controlled by two interacting genes localized within the H-2 complex. Thus, F1 hybrids prepared between parental low responder strains could yield high level immune responses. In addition, strains bearing recombinant H-2 haplotypes were used to map the two distinct genes controlling the immune response. The alleles at each locus were shown to be highly polymorphic as evidenced by the asymmetric complementation patterns observed. The restricted interactions of specific alleles was termed coupled complementation. The significance of the results in the terms of mechanisms of Ir gene control are discussed. ...

In this thesis I present my investigations of two candidate genes, CIITA and VAV1, in these diseases. CIITA is the major control factor for transcription of the HLA class II genes, and associated to all three diseases. In paper I we demonstrate genotype variation for markers in the CIITA gene, depending on age among healthy controls. This finding is also replicated in an independent cohort. The consequence of this can be faulty conclusions in association studies, and hence age should be corrected for in genetic case-control studies. We find that association to T1D remains after controlling for age for rs11074932 (p=0.004) and rs3087456 (p=0.001), two markers in the promoter area that also are found to associate to RA but for the opposite allele (paper III). In paper II we replicate the previously reported association between CIITA rs4774 and MS in cases carrying the HLADRB1*15 allele (p=0.01, OR: 1.21) but also report association to MS for the same marker when stratifying for the MS protective ...

Antibodies for proteins involved in MHC class II receptor activity pathways, according to their Panther/Gene Ontology Classification

MHC II glycoproteins are only present on specialised antigen-presenting cells (APCs), including macrophages that engulf foreign particles such as bacteria, dendritic cells that present antigen to T cells, and B cells that produce antibodies.. ...

Such controversial results as well as the fact that some people bearing G/G genotype of CTLA-4 ... close association with MHC class II alleles [12].

Interactions between Antigen Presenting Cells and T-cells at cellular and molecular level. MHC-I and MHC-II expressions and interactions with T-cells.

Background: The vulnerability to a severe viral infection reported to be associated with genetic variants in immune response genes using case reports and studies GWAS. SARS-CoV-2 is a viral disease that appears that caused millions of COVID 19 cases worldwide. Read more…. ...

The genetic blueprint contains many genes that promote health as well as many genes that cause disease. With a view to increasing the specificity and safety of gene targeting by homeopathic DNA, (because homeopathic DNA, which is of undefined sequence, induces various disease symptoms in healthy people) Drs. Jenaer and Marichal pioneered the use of highly diluted small DNA molecules with well-defined sequences to target immune response genes and fight infections. Their system, called Micro-Immunotherapy proved to be very effective. The Homeovitality system was developed along the same lines as Micro-Immunotherapy ...