The basic pattern of MHC variation in fish, with MHC class I versus class II, and polymorphic classical versus nonpolymorphic nonclassical, is similar in fish and mammals. Nevertheless, in many or all teleost fishes, important differences with mammalian or human MHC were observed: (1) The allelic/haplotype diversification levels of classical MHC class I genes tend to be much higher than in mammals; (2) Teleost fish classical MHC class I and class II loci are not linked. The present article summarizes previous studies that performed quantitative trait loci (QTL) analysis for mapping differences in teleost fish disease resistance, and discusses them from MHC point of view. Overall, those studies suggest the possible importance of genomic regions including classical MHC class II and nonclassical MHC class I genes, whereas similar observations were not made for the genomic regions with the highly diversified classical MHC class I alleles. The present study is a review and discussion of the fish MHC
In neuroblastoma, N-myc suppresses the expression of major histocompatibility complex (MHC) Class I antigens by reducing the binding of a nuclear factor to the enhancer-A element in the MHC Class I gene promoter. We show here that the p50 subunit of NF-kappa B is part of this complex and that expres …
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Tumor cell-based vaccines are currently used in clinical trails, but they are in general poorly immunogenic because they are composed of cell extracts or apoptotic cells. Live tumor cells should be much better Ags provided that they are properly processed by the host immune system. We show herein that stable expression of a small hairpin RNA for ERK5 (shERK5) decreases ERK5 levels in human and mouse leukemic cells and leads to their elimination by NK cells in vivo. The shERK5 cells show down-regulation of MHC class I expression at the plasma membrane. Accordingly, ectopic activation of the ERK5 pathway induces MHC class I gene expression. Coinjection of shERK5-expressing cells into the peritoneum diminishes survival of engrafted wild-type tumor cells. Moreover, s.c. injection of shERK5-expressing cells strongly diminishes tumor development by wild-type cells. Our results show that shERK5 expression in leukemia cells effectively attenuates their tumor activity and allows their use as a tumor cell-based
Somatic cell nuclear transfer (SCNT), or cloning, is a form of artificial reproductive technology that can be used to improve economic traits of domestic animals. However, extreme inefficiency of producing viable offspring via this method is a major limitation. An aggressive immune response at the maternal-fetal interface is an important reason for SCNT pregnancy loss. The goal of this project was to investigate the molecular mechanisms of immune-mediated miscarriage in cloned cattle pregnancies. Many publications hint that immune-mediated miscarriage is associated with abnormal MHC-I expression in the placenta. The regulation of bovine MHC-I genes was systematically studied to identify the cause of abnormal MHC-I expression during immune-mediated miscarriage. We also produced cloned pregnancies to study immune- mediated pregnancy loss. MHC-I and cytokines involved in proinflammatory responses were highly expressed in the placental trophoblast cells of cloned fetuses and in the uterine endometrium of
The aim of this project was to isolate a functional BoLA class I gene, to transfect this into L cells and to investigate the possibility of a second BoLa class I locus. Attempts to isolate a functional BoLA class I gene from a cosmid library were unsuccessful, but clones encoding complete BoLA genes were successfully identified from a bacteriophage library. This library was made from animal 10769 which has BoLA type w10/w11 and the genes were identified with a class I cDNA probe, pBoLA-1. These clones were transfected into mouse L cells to look for expression. One of the clones, 19.1, expressed class I molecules when analysed by indirect immunofluorescence on the FACScan and by fluorescence microscopy. The Northern blot analysis confirmed class I transcription products when probed with pBoLA-1. Clone 19.1 was identified as encoding a w11 gene by a microlymphocytotoxicity test. Also in a T cell cytotoxicity assay, Ltk 19.1 cells were killed by alloreactive anti w11 cytotoxic T cell clones but not ...
Polymorphisms located within the MHC have been linked to many disease outcomes by mechanisms not yet fully understood in most cases. Variants located within untranslated regions of HLA genes are involved in allele-specific expression and may therefore underlie some of these disease associations.. We determined sequences extending nearly 2 kb upstream of the transcription start site for 68 alleles from 57 major lineages of classical HLA class I genes. The nucleotide diversity within this promoter segment roughly follows that seen within the coding regions, with HLA-B showing the highest (?1.9%), followed by HLA-A (?1.8%), and HLA-C showing the lowest diversity (?0.9%). Despite its greater diversity, HLA-B mRNA expression levels determined in 178 European Americans do not vary in an allele- or lineage-specific manner, unlike the differential expression levels of HLA-A or HLA-C reported previously.. Close proximity of promoter sequences in phylogenetic trees is roughly reflected by similarity of ...
In Ad12 tumorigenic cells, surface levels of the major histocompatibility class I antigens become greatly diminished, enabling these cancerous cells to escape immunosurveillance by cytotoxic T lymphocytes. Weve shown that the E1A-12 protein mediates this effect by altering the binding of two transcription factors (NF-kB and COUP-TF) to the class I enhancer which, in turn, blocks transcription from the class I promoter. Specifically, the activator NF-kB becomes hypophosphorylated on a specific residue (serine 337) that disables it from binding to its cognate recognition site on the class I enhancer. This finding alone provided a new dimension into how NF-kB, the major regulator of genes involved in immune defense, can modulate gene expression. In addition, the repressor COUP-TF becomes strongly bound to a different recognition site on the class I enhancer, where it associates with a histone deacetylase (HDAC) and E1A-12, resulting in chromatin compaction. In this way, E1A-12 mediates global ...
We identified B-G-like genes in the whooping and Florida sandhill cranes and linked them to the major histocompatibility complex (MHC). We evaluated the inheritance of B-G-like genes in families of whooping and Florida sandhill cranes using restriction fragment patterns (RFPs). Two B-G-like genes, designated wcbgl and wcbg2, were located within 8 kb of one another. The fully sequenced wcbg2 gene encodes a B-G IgV-like domain, an additional Ig-like domain, a transmembrane domain, and a single heptad domain typical of -helical coiled coils. Patterns of restriction fragments in DNA from the whooping crane and from a number of other species indicate that the B-G-like gene families of cranes are large with diverse sequences. Segregation of RFPs in families of Florida sandhill cranes provide evidence for genetic polymorphism in the B-G-like genes. The restriction fragments generally segregated in concert with MHC haplotypes assigned by serological typing...
The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped t …
Description: The butyrophilin (BTN) genes are a group of major histocompatibility complex (MHC)-associated genes that encode type I membrane proteins with 2 extracellular immunoglobulin (Ig) domains and an intracellular B30.2 (PRYSPRY) domain. Three subfamilies of human BTN genes are located in the MHC class I region: the single-copy BTN1A1 gene (MIM 601610) and the BTN2 (e.g., BTN2A1; MIM 613590) and BTN3 (e.g., BNT3A1) genes, which have undergone tandem duplication, resulting in 3 copies of each (summary by Smith et al., 2010 [PubMed 20208008]). NCBI Entrez Gene , GeneCards , Harmonizome ...
MHC Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. MHC class I…
MHC Class I Qa.m2, 0.5 ml. The Qa region, so named because of the closely linked Qa 1-9 loci, is situated on murine chromosome 17 between the H-2D and T1a loci.
article{f66fe82b-15d5-4f5b-963e-718069cb47dc, abstract = {,p,The assembly of MHC class I molecules is regulated by a multi-protein complex in the endoplasmic reticules (ER) termed the loading complex. Tapasin is suggested to be one of the molecules forming this complex on the basis of its interaction with both the transporter associated with antigen processing (TAP) and MHC class I molecules. To address whether TAP is indispensable for the processing of the assembly of tapasin-associated MHC class I molecules, we studied the association of MHC class I molecules with tapasin, the assembly of tapasin-associated MHC class I with peptides and the peptide-mediated dissociation of MHC class I from tapasin in TAP-mutant T2 cells. In the absence of TAP, MHC class I heavy chain and beta(2)-microglobulin dimers were found to be properly associated with tapasin. The stable MHC class I dimer was required for its association with tapasin in the ER. In the absence of TAP, tapasin retained MHC class I ...
Homologues of the human being major histocompatibility complex (MHC) loci are present in all the Catarrhini (Old World primates, apes, and humans), and some of their allelic lineages have survived several speciation events. loci in genera of this phyletic group. Additionally, the Callitrichinae genera exhibit limited variability of their MHC class I genes, in contrast to the high variability displayed by all other primates. Each Callitrichinae genus, therefore, expresses its own set of MHC class I genes, suggesting that an unusually Taxol inhibition high rate of turnover of loci occurs in this subfamily. The limited variability of MHC class I genes in the Callitrichinae is likely the result of the recent origin of these loci. Among the hallmarks of the main histocompatibility complicated (MHC) may be the high polymorphism and intralocus variability of its loci (1). At the individual classical MHC course I locus are remarkably well preserved through the entire infraorder Catarrhini (Aged Globe ...
Chimpanzees have got orthologs of the six, fixed, functional human genes. cytoplasmic tails. Systematic mutagenesis showed that each substitution contributes changes in cell-surface expression. The combination of residues present in Patr-AL appears unique, but each individual residue is present in other primate MHC class I molecules, notably MHC-E, the most ancient of Gusb the functional human MHC class I molecules. INTRODUCTION The selective pressures imposed by diverse, fast-evolving pathogens cause the MHC class I genes of their mammalian hosts also to evolve rapidly (1). As a consequence there is considerable species-specific character to gene families. Characteristics shared by most mammalian species are highly polymorphic classical MHC class I molecules that engage highly variable types of lymphocyte receptor and conserved non-classical MHC class I molecules that engage conserved types of lymphocyte receptors. Of the six human genes that are functional, and are highly polymorphic and ...
HLA class I histocompatibility antigen, alpha chain F is a protein that in humans is encoded by the HLA-F gene. The Major Histocompatibility Complex (MHC) is a group of cell surface proteins that in humans is also called the Human Leukocyte Antigen (HLA) complex. These proteins are encoded by a cluster of genes known as the HLA locus. The HLA locus occupies a ~ 3Mbp stretch that is located on the short arm of chromosome 6, specifically on 6p21.1-21.3. The MHC proteins are classified into three main categories, namely class I, II, and III. There are over 140 genes within the HLA locus and they are often called HLA genes. HLA-A, B, and C are the classical class I genes and HLA-E, F and G are the nonclassical class I genes. The protein encoded from the gene HLA-F was originally isolated from the human lymphoblastoid cell line 721. The HLA-F gene is located on the short arm of chromosome 6, telomeric to the HLA-A locus. HLA-F has little allelic polymorphism and is highly conserved in other primates. ...
HLA-G histocompatibility antigen, class I, G, also known as human leukocyte antigen G (HLA-G), is a protein that in humans is encoded by the HLA-G gene. HLA-G belongs to the HLA nonclassical class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. HLA-G is expressed on fetal derived placental cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exon 6 encodes the cytoplasmic tail. Exon 7 and 8 are not translated due to a stop codon present in exon 6. HLA-G may play a role in immune tolerance in pregnancy, being expressed in the placenta by extravillous trophoblast cells (EVT), while the classical MHC class I genes (HLA-A and HLA-B) are not. As HLA-G ...
The role of exocytosis of major histocompatibility complex (MHC) class I molecules in the presentation of antigens to mouse cytotoxic T lymphocytes (CTLs) was examined by use of a recombinant vaccinia virus that expresses the E19 glycoprotein from adenovirus. E19 blocked the presentation of vaccinia and influenza virus proteins to CTLs in a MHC class I allele-specific manner identical to its inhibition of MHC class I transport from the endoplasmic reticulum. This finding indicates that (i) the relevant parameter for antigen presentation is the rate of MHC class I molecule exocytosis, not the level of class I cell surface expression, and (ii) association of class I molecules with antigen is likely to occur within the endoplasmic reticulum. ...
In this study, we describe the creation of class I MHC-deficient pigs by simultaneously disrupting seven alleles of classical class I SLA genes. At the time of publication, the animals have been healthy and growing well for 7 mo. All cell types tested from these animals exhibit total loss of cell surface class I MHC proteins. Inactivation of a single gene, β2m, also prevents expression of class I MHC heterotrimers at the cell surface. This disruption was not attempted because mice lacking β2m lose the ability to regulate iron homeostasis (30-32). The high efficiency of the gRNA/Cas9 technology enabled the rapid production of animals deficient in class I MHC. The relative ease of this approach may enable the rapid production of many novel species lacking class I MHC gene activity.. Multigene families can be difficult to analyze because of functional redundancies. Simultaneous inactivation of all related genes minimizes these challenges by creating a null background that enables the study of one ...
BY55 is a human cell surface molecule whose expression is restricted to NK cells, a subset of circulating CD8+ T lymphocytes, and all intestinal intraepithelial T lymphocytes. Here, we report that BY55 is a novel NK receptor showing broad specificity for both classical and nonclassical MHC class I molecules, and that optimal binding requires a prior aggregation of MHC class I complexes. Using BY55 transfectants, we have identified functional consequences of MHC class I/ligand interactions for the class I-bearing cell. The triggering of MHC class I molecules on human T cell clones by BY55 delivered a potent proliferative signal in the presence of soluble CD3 mAb. The costimulatory signal provided by MHC class I ligation was only seen in activated, and not resting, peripheral blood T cells. This observation represents an additional and/or alternative pathway to CD28 costimulation and may be of particular relevance in memory T cells lacking CD28, such as intestinal intraepithelial T lymphocytes, which are
Little is known about the structure of major histocompatibility complex (MHC) molecules outside of mammals. Only one class I molecule in the chicken MHC is highly expressed, leading to strong genetic associations with infectious pathogens. Here, we report two structures of the MHC class I molecule BF2*2101 from the B21 haplotype, which is known to confer resistance to Mareks disease caused by an oncogenic herpesvirus. The binding groove has an unusually large central cavity, which confers substantial conformational flexibility to the crucial residue Arg9, allowing remodeling of key peptide-binding sites. The coupled variation of anchor residues from the peptide, utilizing a charge-transfer system unprecedented in MHC molecules, allows peptides with conspicuously different sequences to be bound. This promiscuous binding extends our understanding of ways in which MHC class I molecules can present peptides to the immune system and might explain the resistance of the B21 haplotype to Mareks disease.
Anti Mouse MHC Class I H-2Kb Antibody, clone AF6-88.5 , Mouse Anti-Mouse Monoclonal Antibody validated in IHC-F, FC, IP (ABD12625), Abgent
We describe here the isolation and sequencing of a previously uncharacterized HLA class I gene. This gene, HLA-5.4, is the third non-HLA-A,B,C gene characterized whose sequence shows it encodes an intact class I protein. RNase protection assays with a probe specific for this gene demonstrated its expression in B lymphoblastoid cell lines, in resting T cells, and skin cells, while no mRNA could be detected in the T cell line Molt 4. Consistent with a pattern of expression different from that of other class I genes, DNA sequence comparisons identified potential regulator motifs unique to HLA-5.4 and possibly essential for tissue-specific expression. Protein sequence analysis of human and murine class I antigens has identified 10 highly conserved residues believed to be involved in antigen binding. Five of these are altered in HLA-5.4, and of these, three are nonconservative. In addition, examination of the HLA-5.4 DNA sequence predicts that the cytoplasmic segment of this protein is shorter than ...
Motivation: MHC:peptide binding plays a central role in activating the immune surveillance. Computational approaches to determine T-cell epitopes restricted to any given major histocompatibility complex (MHC) molecule are of special practical value in the development of for instance vaccines with broad population coverage against emerging pathogens. Methods have recently been published that are able to predict peptide binding to any human MHC class I molecule. In contrast to conventional allele-specific methods, these methods do allow for extrapolation to uncharacterized MHC molecules. These pan-specific human lymphocyte antigen (HLA) predictors have not previously been compared using independent evaluation sets.. Result: A diverse set of quantitative peptide binding affinity measurements was collected from Immune Epitope database (IEDB), together with a large set of HLA class I ligands from the SYFPEITHI database. Based on these datasets, three different pan-specific HLA web-accessible ...
Major histocompatibility complex (MHC) class I molecules present peptides derived from the endogenous protein pool to cytotoxic T lymphocytes, which can thus recognize intracellular antigen. This pathway may depend on a transporter (PSF1) to mediate entry of the cytosolic peptides into a pre-Golgi compartment where they bind to class I heavy chains and promote their stable assembly with beta 2-microglobulin. There is, however, only indirect support for this function of PSF1. Here we show that PSF1 is necessary for the efficient assembly of class I molecules and enables them to present a peptide epitope derived from endogenously synthesized viral antigen. Immunochemical and genetic data demonstrate that the PSF1 polypeptide is associated with a complementary transporter chain, which is polymorphic and is encoded by the PSF2 gene, which is closely linked to PSF1.
Detailed description of cellular interactions including MHC classes, HLA, MHC class I gene complex, MHC class II gene complex and MHC Class III gene complex.
We describe here the isolation and sequencing of a previously uncharacterized HLA class I gene. This gene, HLA-5.4, is the third non-HLA-A,B,C gene characterized whose sequence shows it encodes an intact class I protein. RNase protection assays with a probe specific for this gene demonstrated its expression in B lymphoblastoid cell lines, in resting T cells, and skin cells, while no mRNA could be detected in the T cell line Molt 4. Consistent with a pattern of expression different from that of other class I genes, DNA sequence comparisons identified potential regulator motifs unique to HLA-5.4 and possibly essential for tissue-specific expression. Protein sequence analysis of human and murine class I antigens has identified 10 highly conserved residues believed to be involved in antigen binding. Five of these are altered in HLA-5.4, and of these, three are nonconservative. In addition, examination of the HLA-5.4 DNA sequence predicts that the cytoplasmic segment of this protein is shorter than ...
The molecular definition of tumor antigens recognized by cytolytic T lymphocytes (CTL) started in the late 1980s, at a time when the MHC class I antigen processing field was in its infancy. Born together, these two fields of science evolved together and provided each other with critical insights. Over the years, stimulated by the potential interest of tumor antigens for cancer immunotherapy, scientists have identified and characterized numerous antigens recognized by CTL on human tumors. These studies have provided a wealth of information relevant to the mode of production of antigenic peptides presented by MHC class I molecules. A number of tumor antigenic peptides were found to result from unusual mechanisms occurring at the level of transcription, translation or processing. Although many of these mechanisms occur in the cell at very low level, they are relevant to the immune system as they determine the killing of tumor cells by CTL, which are sensitive to low levels of peptide/MHC complexes.
Transcriptional activator. Binds to the interferon-stimulated response element (ISRE) of the MHC class I promoter. Binds the immunoglobulin lambda light chain enhancer, together with PU.1. Probably plays a role in ISRE-targeted signal transduction mechanisms specific to lymphoid cells. Involved in CD8(+) dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5-TGAnTCA/GAAA-3), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF4 and activation of genes.
|strong|Mouse anti Sheep MHC Class I monoclonal antibody, clone VPM19|/strong| recognizes the ovine homologue of the human MHC Class I, a monomorphic determinant expressed on the heavy chain of sheep …
Purpose: We hypothesized that T-cell immune interaction affects tumor development and thus clinical outcome. Therefore, we examined the clinical impact of human leukocyte antigen (HLA) class I tumor cell expression and regulatory T-cell (Treg) infiltration in breast cancer.. Experimental Design: Our study population (N = 677) is consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1994. Formalin-fixed, paraffin-embedded tumor tissue was immunohistochemically stained using HCA2, HC10, and Foxp3 monoclonal antibodies.. Results: HLA class I expression was evaluated by combining results from HCA2 and HC10 antibodies and classified into three groups: loss, downregulation, and expression. Remarkably, only in patients who received chemotherapy, both presence of Treg (P = 0.013) and higher HLA class I expression levels (P = 0.002) resulted in less relapses, independently of other variables. Treg and HLA class I were not of influence on clinical ...
Reduced surface expression of MHC class I antigens in different subsets of STAT1−/− lymphocytes. Freshly isolated lymphocytes from thymi (A) or lymph nodes
Split immunological tolerance refers to states in which an individual is capable of mounting certain types of immune responses to a particular antigenic challenge, but is tolerant of the same antigen in other compartments of the immune system. This concept is applicable to the immunological relationship between mother and fetus, and particularly relevant in equine pregnancy. In pregnant mares, antibody responses to paternal foreign Major Histocompatibility Complex class I antigens are robust, while anti-paternal cytotoxic T cell responses are diminished compared to those mounted by non-pregnant mares. Here, we compared the distribution of the major lymphocyte subsets, the percentage of lymphocytes expressing Interferon Gamma (IFNG) and Interleukin 4 (IL4) and the level of expression of the immunoregulatory transcription factor FOXP3 between pregnant and non-pregnant mares, and between peripheral blood and the endometrium during pregnancy. In a cohort of mares in which peripheral blood lymphocytes were
We describe here the isolation and sequencing of a previously uncharacterized HLA class I gene. This gene, HLA-5.4, is the third non-HLA-A,B,C gene characterize
The major histocompatibility complex (MHC) encodes proteins that are central for antigen presentation and pathogen elimination. MHC class I (MHC-I) genes have attracted a great deal of interest among
MHC Class I Expression by Donor Hematopoietic Stem Cells Is Required to Prevent NK Cell Attack in Allogeneic, but Not Syngeneic Recipient Mice. NK cells resist engraftment of syngeneic and allogeneic bone marrow (BM) cells lacking major histocompatibility (MHC) class I molecules, suggesting a critical role for donor MHC class I molecules.... ...
MHC class I大鼠单克隆抗体[ERMP42](ab15680)可与小鼠样本反应并经IHC, Flow Cyt实验严格验证,被1篇文献引用并得到2个独立的用户反馈。所有产品均提供质保服务,中国75%以上现货。
Speaker: Jaqcues Neefjes, Division of Cell Biology, Netherlands Cancer InstituteTitle: How MHC class I selects peptides and novel proteins in the MHC pathway identified by a unique genome-wide screenHost: Rikard Holmdal
Clone REA619 recognizes the mouse H-2Db MHC class I alloantigen expressed on mouse MHC class I+ cells of the H-2Db haplotype. Reactivity to other haplotypes like, for example, a, d, f, k, n, p, q, r, s, u, and v, has not been observed. Additional information: Clone REA619 displays negligible binding to Fc receptors. - USA
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Anderson HA, Chen Y, Norkin LC. 1998. MHC class I molecules are enriched in caveolae but do not enter with simian virus 40.. J Gen Virol. 79 ( Pt 6):1469-77. ...
Free resource for searching and exporting immune epitopes. Includes more than 95% of all published infectious disease, allergy, autoimmune, and transplant epitope data.
Each and every citizen who has a citizenship id is permitted to stay in the country. Similarly, each and every cell who has a proper MHC class I is permitted to stay in the body.) ...
as a geometry that consists of a single patch that is associated with a single exterior boundary and zero or more interior boundaries. ...
瀰漫性泛細支氣管炎是一種特發病(英语:Idiopathy),即是說它的生理、環境及病原體成因仍是未知的。然而,已知有幾個因素有可能與致病機制(英语:Pathogenesis)有關[4]。 主要組織相容性複合體(MHC)是存在於大部份脊椎動物的一個基因家族,與免疫系統相關。其中人類的位於6號染色體上。當中一部份為人類白細胞抗原(HLA),負責控制抗原呈現系統,是人類對付如細菌和病毒等病原體的後天免疫系統的一部份。當人類細胞受到病原體感染時,它們能在它們的表面上呈現部份病原體蛋白質;這就是抗原呈現。受感染的細胞因此成為細胞毒性T細胞的攻擊對象,它們會把受感染的細胞殺死,並將它們從體內移除[8]。 瀰漫性泛細支氣管炎感病性的遺傳預先傾向性(英语:Genetic ...
TY - JOUR. T1 - Expression of the major histocompatibility complex class I molecule Mamu-A*01 is associated with control of simian immunodeficiency virus SIVmac239 replication. AU - Mothé, Bianca R.. AU - Weinfurter, Jason. AU - Wang, Chenxi. AU - Rehrauer, William. AU - Wilson, Nancy. AU - Allen, Todd M.. AU - Allison, David B.. AU - Watkins, David. PY - 2003/2/1. Y1 - 2003/2/1. N2 - Several HLA alleles are associated with attenuated human immunodeficiency virus disease progression. We explored the relationship between the expression of particular major histocompatibility complex (MHC) class I alleles and viremia in simian immunodeficiency virus SIVmac239-infected macaques. Of the common MHC class I alleles, animals that expressed Mamu-A*01 exhibited the best control of viral replication.. AB - Several HLA alleles are associated with attenuated human immunodeficiency virus disease progression. We explored the relationship between the expression of particular major histocompatibility complex ...
TY - JOUR. T1 - A computational resource for the prediction of peptide binding to Indian rhesus macaque MHC class I molecules. AU - Peters, B.. AU - Bui, H. H.. AU - Sidney, J.. AU - Weng, Z.. AU - Loffredo, J. T.. AU - Watkins, D. I.. AU - Mothé, B. R.. AU - Sette, A.. PY - 2005/11/1. Y1 - 2005/11/1. N2 - Non-human primates, in general, and Indian rhesus macaques, specifically, play an important role in the development and testing of vaccines and diagnostics destined for human use. To date, several frequently expressed macaque MHC molecules have been identified and their binding specificities characterized in detail. Here, we report the development of computational algorithms to predict peptide binding and potential T cell epitopes for the common MHC class I alleles Mamu-A*01, -A*02, -A*11, -B*01 and -B*17, which cover approximately two thirds of the captive Indian rhesus macaque populations. We validated this method utilizing an SIV derived data set encompassing 59 antigenic peptides. Of all ...
Mhc class I molecules display intracellularly derived peptides on the surface of almost all nucleated mammalian cells for recognition by the immune system. MHC class I heavy chain, which contains the peptide binding site, is a classical type I transmembrane protein with a large luminal/extracellular domain and a short cytosolic tail. The heavy chain enters the secretory pathway via the ER translocon, a channel whose major component is Sec61. The light chain β2 microglobulin (β2m)1 and the peptide associate with the heavy chain after it has been inserted into the ER membrane, and the complex is then transported, via the Golgi, to the plasma membrane. In humans, the MHC class I heavy chain is a 43-kD protein that contains a single N-linked glycan.. Human cytomegalovirus (HCMV) evades detection by the immune system by targeting MHC class I heavy chains for destruction soon after they have been synthesized. The HCMV proteins responsible for MHC class I heavy chain destruction are US11 and US2 ...
Background: A major group of murine inhibitory receptors on Natural Killer (NK) cells belong to the Ly49 receptor family and recognize MHC class I molecules. Infected or transformed target cells frequently downmodulate MHC class I molecules and can thus avoid CD8(+) T cell attack, but may at the same time develop NK cell sensitivity, due to failure to express inhibitory ligands for Ly49 receptors. The extent of MHC class I downregulation needed on normal cells to trigger NK cell effector functions is not known. Methodology/Principal Findings: In this study, we show that cells expressing MHC class I to levels well below half of the host level are tolerated in an in vivo assay in mice. Hemizygous expression (expression from only one allele) of MHC class I was sufficient to induce Ly49 receptor downmodulation on NK cells to a similar degree as homozygous expression, despite a strongly reduced cell surface level of MHC class I. Co-expression of weaker MHC class I ligands in the host did not have any ...
Background A major group of murine inhibitory receptors on Natural Killer (NK) cells belong to the Ly49 receptor family and recognize MHC class I molecules. Infected or transformed target cells frequently downmodulate MHC class I molecules and can thus avoid CD8+ T cell attack, but may at the same time develop NK cell sensitivity, due to failure to express inhibitory ligands for Ly49 receptors. The extent of MHC class I downregulation needed on normal cells to trigger NK cell effector functions is not known. Methodology/Principal Findings In this study, we show that cells expressing MHC class I to levels well below half of the host level are tolerated in an in vivo assay in mice. Hemizygous expression (expression from only one allele) of MHC class I was sufficient to induce Ly49 receptor downmodulation on NK cells to a similar degree as homozygous expression, despite a strongly reduced cell surface level of MHC class I. Co-expression of weaker MHC class I ligands in the host did not have any further
Human cytomegalovirus encodes two glycoproteins, US2 and US11, which cause rapid degradation of MHC class I molecules, thus preventing recognition of virus-infected cells by the immune system. This degradation process involves retrograde transport or dislocation of MHC class I molecules from the endoplasmic reticulum (ER) to the cytosol, where they are deglycosylated by an N-glycanase and degraded by the proteasome. At present it is unknown whether ubiquitination is required for US2- and US11-mediated dislocation and degradation of MHC class I molecules. Here, we show that in E36ts20 hamster cells, which contain a temperature-sensitive mutation in the E1 ubiquitin-activating enzyme, US11-mediated degradation of MHC class I molecules is strongly impaired at the non-permissive temperature, indicating the necessity for ubiquitination in this process. We next addressed the question of whether ubiquitination is a condition for the retrograde movement of MHC class I molecules from the ER to the ...
Understanding the structure and variability of adaptive loci such as the major histocompatibility complex (MHC) genes is a primary research goal for evolutionary and conservation genetics. Typically, classical MHC genes show high polymorphism and are under strong balancing selection, as their products trigger the adaptive immune response in vertebrates. Here, we assess the allelic diversity and patterns of selection for MHC class I and class II loci in a threatened shorebird with highly flexible mating and parental care behaviour, the Snowy Plover (Charadrius nivosus) across its broad geographic range. We determined the allelic and nucleotide diversity for MHC class I and class II genes using samples of 250 individuals from eight breeding population of Snowy Plovers. We found 40 alleles at MHC class I and six alleles at MHC class II, with individuals carrying two to seven different alleles (mean 3.70) at MHC class I and up to two alleles (mean 1.45) at MHC class II. Diversity was higher in the peptide
The results presented here add a critical lineage to the emerging picture of MHC evolution in amniotes, with a genome-level characterization of MHC organization in an evolutionarily divergent reptile, the tuatara. The tuatara MHC region appears to be large with a high repeat content. We found a total of seven class I sequences and 11 class II β sequences, but some appeared to represent pseudogenes. Chromosome 13q appears to contain the core MHC, as clones containing classical class I, class II beta, and class II alpha chain genes map to here, but additional class I genes were located chromosome 4p.. The MHC in tuatara has low gene density compared with other species. We found at most five genes on individual BAC clones, and many clones contained only one or two genes and a high number of repetitive elements. The low density of tuatara MHC genes is a likely reason for challenges in identifying other MHC-associated genes like TAP1, TAP2, TAPBP, or C4 or framework genes like DAXX, BRD2, or TNXB on ...
Mouse anti Mouse MHC Class I H-2Kd antibody, clone K3 recognizes the murine MHC Class I H-2Kd haplotype. The major histocompatibility comp
Fascinating recent discoveries have focused attention on the nonclassical class I molecules. They can exert their function at most levels of the immune response, being part of both innate and adaptive immune systems. They not only have specialized antigen-presentation functions but also play important immunoregulatory roles: HLA-E regulates natural killer cells by interacting with CD94/NKG2 receptors; the MIC (MHC class I chain related) glycoproteins appear crucial to the activation of gammadelta T cells in the gastrointestinal epithelium; HLA-G may play a role in controlling the immune response to the fetus; and CD1 molecules are important in defense against bacterial infections, as well as in the development and regulation of a subset of NKT cells expressing a highly restricted TCR repertoire; however not all nonclassical class I molecules have an immunological function, as demonstrated by HFE which is implicated in iron metabolism.
Circumstantial evidence for transfer of MHC molecules between cells of the immune system was reported already 30 y ago (25, 26). More recent data have conclusively shown that effector T cells acquire both MHC class I and II molecules from APC (11, 12, 27). Also, B cells acquire membrane antigens from surrounding cells, a phenomenon which is followed by a very efficient presentation of these antigens to T cells (10). We show here for the first time that receptor-mediated ligand acquisition occurs also for NK cells, both in vitro and in vivo. Inhibitory Ly49 receptors on NK cells specifically acquired MHC class I molecules from surrounding cells, both when normal NK cells were transferred into a host expressing the ligand for the Ly49 molecule analyzed, and also in vitro when cells transfected with Ly49A were cocultured with cells transfected with H-2Dd. Ligand acquisition was a very rapid event, occurring within 30 min in both systems. The amount of acquired molecules remained high as long as the ...
TY - JOUR. T1 - Location of the epitope for an anti-CD8α antibody 53.6.7 which enhances CD8α-MHC class I interaction indicates antibody stabilization of a higher affinity CD8 conformation. AU - Devine, Lesley. AU - Hodsdon, Michael E.. AU - Daniels, Mark A.. AU - Jameson, Stephen C. AU - Kavathas, Paula B.. PY - 2004/5/15. Y1 - 2004/5/15. N2 - MHC class I tetramers are widely used, usually in combination with an antibody to CD8, to detect antigen specific T cells. Some anti-CD8α antibodies block the interaction of murine MHC class I tetramers with CD8 T cells, while others such as 53.6.7, enhance. To understand the molecular basis for this effect, we mapped the epitope for the enhancing antibody 53.6.7 and three other blocking antibodies using a panel of murine CD8α (Lyt-2) mutants expressed on COS-7 transfectants. Mutations in residues that contact MHC class I affected binding of the blocking antibodies. In contrast, antibody 53.6.7 was affected by a mutation in the residue T81A located on ...
Author(s): Chen, Keling | Advisor(s): Shastri, Nilabh | Abstract: Cytotoxic T cells monitor MHC class I complexes on antigen presenting cells for the potential presence of any non-self peptides that could derive from viral infection or cancerous cells. Effective immune surveillance requires that MHC class I molecules display a peptide repertoire on the surface representing all cellular proteins. This ensures that foreign antigens from all sources are presented. How the peptide repertoire can be comprehensive despite the large differences in abundance and stability of individual proteins is not known. The pioneer round of translation is the first round of translation that occurs on newly spliced mRNA. It is associated with nonsense-mediated decay of mRNAs, allowing cells to detect and eliminate the aberrant mRNAs containing premature stop codons. We showed here that the peptide presentation by MHC I molecules was strongly influenced by the pioneer round of translation. Inhibition of the pioneer round of
TY - JOUR. T1 - Mamu-A*01/Kb transgenic and MHC Class I knockout mice as a tool for HIV vaccine development. AU - Li, Jinliang. AU - Srivastava, Tumul. AU - Rawal, Ravindra. AU - Manuel, Edwin. AU - Isbell, Donna. AU - Tsark, Walter. AU - La Rosa, Corinna. AU - Wang, Zhongde. AU - Li, Zhongqi. AU - Barry, Peter A. AU - Hagen, Katharine D.. AU - Longmate, Jeffrey. AU - Diamond, Don J.. PY - 2009/4/25. Y1 - 2009/4/25. N2 - We have developed a murine model expressing the rhesus macaque (RM) Mamu-A*01 MHC allele to characterize immune responses and vaccines based on antigens of importance to human disease processes. Towards that goal, transgenic (Tg) mice expressing chimeric RM (α1 and α2 Mamu-A*01 domains) and murine (α3, transmembrane, and cytoplasmic H-2Kb domains) MHC Class I molecules were derived by transgenesis of the H-2KbDb double MHC Class I knockout strain. After immunization of Mamu-A*01/Kb Tg mice with rVV-SIVGag-Pol, the mice generated CD8+ T-cell IFN-γ responses to several known ...
The 25-D1.16 monoclonal antibody reacts with mouse MHC class I H-2K|sup|b|/sup| bound to the ovalbumin-derived peptide with sequence SIINFEKL. This antibody does not react with unbound MHC class I H-2K|sup|b|/sup| or MHC class I H-2K|sup|b|/sup| bound to an irrelevant peptide. The 25-D1.16 antibody is often used to track the quantity and localization of antigen-presenting cells bearing these specific molecules |em|in vivo|/em|.
MHC class I molecules display peptides selected from a poorly characterized pool of peptides available in the endoplasmic reticulum. We analyzed the diversity of peptides available to MHC class I molecules by monitoring the generation of an OVA-derived octapeptide, OVA257-264 (SL8), and its C-terminally extended analog, SL8-I. The poorly antigenic SL8-I could be detected in cell extracts only after its conversion to the readily detectable SL8 with carboxypeptidase Y. Analysis of extracts from cells expressing the minimal precursor Met-SL8-I by this method revealed the presence of SL8/Kb and the extended SL8-I/Kb complexes, indicating that the peptide pool contained both peptides. In contrast, cells expressing full length OVA generated only the SL8/Kb complex, demonstrating that the peptide pool generated from the full length precursor contained only a subset of potential MHC-binding peptides. Deletion analysis revealed that SL8-I was generated only from precursors lacking additional C-terminal ...
MHC class I molecules are key in the presentation of antigen and initiation of adaptive CD8+ T cell responses. In addition to its classical activity, MHC I may possess nonclassical functions. We have previously identified a regulatory role of MHC I in TLR signaling and antibacterial immunity. However, its role in innate antiviral immunity remains unknown. In this study, we found a reduced viral load in MHC I-deficient macrophages that was independent of type I IFN production. Mechanically, MHC I mediated viral suppression by inhibiting the type I IFN signaling pathway, which depends on SHP2. Cross-linking MHC I at the membrane increased SHP2 activation and further suppressed STAT1 phosphorylation. Therefore, our data revealed an inhibitory role of MHC I in type I IFN response to viral infection and expanded our understanding of MHC I and antigen presentation.
MHC Class I (H-2Kb) Mouse anti-Mouse, PE, Clone: AF6-88.5.5.3, eBioscience™ 100 μg; PE MHC Class I (H-2Kb) Mouse anti-Mouse, PE, Clone: AF6-88.5.5.3,...
Author Summary HLA class I molecules are expressed on the cell surface of almost all cells of the human body in complex with short fragments (peptides) of cytosolic proteins, thereby providing a snapshot of the intracellular state of a cell to circulating CD8+ T cells. Several processes are involved in shaping the peptide ligand repertoire of an HLA class I molecule, which generally represents only a small fraction of the proteins available in the cytosol. In our work we addressed protein sampling by HLA class I molecules to answer two questions: 1) Which proteins are sampled by the antigen processing pathway and why, and 2) which peptides of a given protein are picked to represent the source protein on the cell surface? To this end we quantified the contribution of each process involved in peptide processing and presentation individually and combined them into a logistic regression model. This simple model enabled us to predict the sampling probability of self proteins and may aid in the identification
In an attempt to establish Macaca fascicularis as a viable animal model for disease studies, characterization of the MHC class I genes is necessary. The necessity arises because the MHC class I molecules have a functional role in immune response. Pig-tailed macaques Macaca nemestrina) and... READ MORE ...
I am running an experiment in which I need to sample all six HLA class I alleles (HLA-A, HLA-B, HLA-C) repeatedly. Is there a dataset online that contains this information? I found this website (http://www.allelefrequencies.net/) but I cannot figure out how to get the data from it in the format that I want. Any help is appreciated. Thank you. EDIT: Sorry, I think the question was a little unclear. What I want to do is have a dataset containing a set of patients, and all 6 of their HLA alleles. Is there such a dataset available somewhere? ...
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Gentaurs MHCE/HLA-E CLIA kit utilizes the Sandwich- CLIA principle. The micro CLIA plate provided in this kit has been pre-coated with an antibody specific to Human MHCE/HLA-E . Standards or samples are added to the micro CLIA plate wells and ...
HIV-1 sequence diversity is affected by selection pressures arising from host genomic factors. Using paired human and viral data from 1071 individuals, we ran ,3000 genome-wide scans, testing for associations between host DNA polymorphisms, HIV-1 sequence variation and plasma viral load (VL), while considering human and viral population structure. We observed significant human SNP associations to a total of 48 HIV-1 amino acid variants (p,2.4 × 10(-12)). All associated SNPs mapped to the HLA class I region. Clinical relevance of host and pathogen variation was assessed using VL results. We identified two critical advantages to the use of viral variation for identifying host factors: (1) association signals are much stronger for HIV-1 sequence variants than VL, reflecting the intermediate phenotype nature of viral variation; (2) association testing can be run without any clinical data. The proposed genome-to-genome approach highlights sites of genomic conflict and is a strategy generally ...
Major histocompatibility complex (MHC) molecules are the core of vertebrates immune system, enabling the distinction between self and non-self or missing-self. MHC class I (MHCI) molecules are central to this function by regulating tolerance and rejection by cytotoxic CD8+ T cells and NK cells. Cellular metabolism, the ensemble of processes fulfilling the bioenergetic and biosynthetic needs of a cell, has been reported to influence MHCI expression in cancer cells. Unpublished data from my own laboratory reveal that an unappreciated correlation between metabolic perturbations and MHCI levels is observed also in non-transformed cells. Based on our preliminary results, we hypothesize that fluctuations in MHCI levels linked to metabolic states serve a twofold purpose. While conforming to the classic definition of self, metabolically abnormal cells can represent a threat for the organism. Fluctuations in MHCI expression might thus modulate the interaction with immune system cells, thereby ...
The enzymes of the ubiquitylation pathway play a pivotal role in a number of cellular processes including regulated and targeted proteosomal degradation of substrate proteins. Three classes of enzymes are involved in the process of ubiquitylation; activating enzymes (E1s), conjugating enzymes (E2s) and protein ligases (E3s). UBA6 is a member of the E1 activating enzyme family and the human gene was first described by Jin et al. (2007). UBA6 shares 42% homology with UBE1 and contains all the structural elements required for E1 enzyme activity (Groettrup et al., 2008). UBA6 interacts with a number of E2 and E3 enzymes and has been shown to be involved with p53 ubiquitylation in vitro (Groettrup et al., 2008; Pelzer et al., 2007). UBA6 activates ubiquitin and the ubiquitin-like protein human leukocyte antigen F-Associated Transcript 10 (FAT10), both of which may serve as a signal for proteasomal degradation. FAT10, is encoded by the major histocompatibility (MHC) class I locus, and its expression ...
CD8+ CTLs are essential for effective immune defense against intracellular microbes and neoplasia. CTLs recognize short peptide fragments presented in association with MHC class I (MHCI) molecules on the surface of infected or dysregulated cells. Ag recognition involves the binding of both TCR and CD8 coreceptor to a single ligand (peptide MHCI [pMHCI]). The TCR/pMHCI interaction confers Ag specificity, whereas the pMHCI/CD8 interaction mediates enhanced sensitivity to Ag. Striking biophysical differences exist between the TCR/pMHCI and pMHCI/CD8 interactions; indeed, the pMHCI/CD8 interaction can be ,100-fold weaker than the cognate TCR/pMHCI interaction. In this study, we show that increasing the strength of the pMHCI/CD8 interaction by ∼15-fold results in nonspecific, cognate Ag-independent pMHCI tetramer binding at the cell surface. Furthermore, pMHCI molecules with superenhanced affinity for CD8 activate CTLs in the absence of a specific TCR/pMHCI interaction to elicit a full range of ...
Mature T lymphocytes of the CD8 or CD4 classes bear αβ T cell receptors (TCR) that are specific for a molecular complex consisting of a major histocompatibility complex class I or II (MHC class I or II) molecule bound to a unique self or foreign peptide
Attention for Chapter 30: Gene-Specific Structures Within Class I Genes from Mus musculus domesticus are Conserved in Class I Genes from Mus pahari ...
The primary immune response to an antigen is initiated through antigen presenting cells such as dendritic cells (DC). Human leukocyte antigens (HLA) on the surface of these cells present protein-derived peptide fragments, where MHC class I associated HLA (i.e. HLA-A, B and C) present peptides to CD8+ T cells and MHC class II associated HLA (HLA-DR, DP and DQ) to CD4+ T cells. MHC-I presentation is fundamental for the development of immunity against tumours and viruses since endogenous proteins are normally presented to CD8+ T cells via this route. Presentation of exogenous antigens via MHC class I can also occur and trigger an immune response. Therefore, the identification of these antigens presented via MHC class I creates huge potential for the generation of new immuno-oncology therapeutics, vaccines and diagnostics.. ...
Mouse monoclonal antibody raised against native MHC Class I. Native purified whole mouse spleen cells. (MAB1363) - Products - Abnova
The monoclonal antibody 6D4 recognizes MICA and MICB, which are transmembrane glycoproteins related to major histocompatibility complex (MHC) class I molecules. In contrast to other MHC class I proteins, MICA/B have no association with β2-microglobulin and do not bind peptides. They are ligands for NKG2D, which is expressed on NK cells and many T cells. MICA/B are expressed on endothelial cells and fibroblasts and are stress-induced in epithelial cells. - USA
Interestingly, weve found that MHC class I molecules are not static entities; they move in a specific way, allowing them to act as immunological sentinels. And because there are many different variants of the MHC class I molecule in the human population, they all have slightly different propensities when it comes to selecting cancer peptides. By collecting this information and building it into computer programmes, we hope to be able to predict exactly which cancer-derived peptides will boost the killer T cells that do the most harm to the tumour, without damaging normal tissue. This will provide a basis for designing better cancer vaccines and may even allow us to select patients who will respond well to checkpoint blockade immunotherapy.. ...
Yin L, Huseby E, Scott-Browne J, Rubtsova K, Pinilla C, Crawford F, Marrack P, Dai S, Kappler JW. A single T cell receptor bound to major histocompatibility complex class I and class II glycoproteins reveals switchable TCR conformers. Immunity. 2011 Jul 22; 35(1):23-33 ...
Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class I molecule:peptide complex. The antigens presented by class I peptides are derived from cytosolic proteins while class II derived from extracellular proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class I proteins presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of cytotoxic T-lymphocytes (CTLs). This mechanism enables CTLs to recognize and eliminate infected cells and tumor cells. In NK-cells, the presence of CD8A homodimers at the cell surface provides a survival mechanism allowing ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
Filagra lowest prices 2 FFilagra Tafra The Breast Center at Anne Arundel Medical Center Annapolis, Maryland. (1992) TAP1 mutant mice are deficient in antigen presentation, surface class I molecules, and CD4в8 T cells. Y.