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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human cytomegalovirus (hCMV) has evolved multiple mechanisms to escape the host immune recognition and innate or adaptive immune responses. Among them, hCMV has developed strategies to modulate the expression and/or function of human leukocyte antigens (HLAs), including by encoding series of infection stage-dependent hCMV proteins to detain and destroy the expression of HLA molecules on the surface of infected cells. This disturbs the antigen presentation and processing, by encoding MHC class I homologues or selective up-regulation of particular HLA class I molecules binding to NK cell inhibitory receptors, and by encoding specific ligand antagonists to interfere with NK cell activating receptors. Here we discussed the molecular mechanisms utilized by the hCMV to alter the formation, transportation and expression of HLA antigens on the infected cell surface. The knowledge about hCMV modulating HLA expression could benefit us to further understand the pathogenesis of viral diseases and may eventually develop novel effective immunotherapies to counteract viral infections and viral associated diseases.
Cell Mol Immunol 2007 Apr
PMID:Modulation of HLA expression in human cytomegalovirus immune evasion. 1748 2

We describe structural studies of the human leukocyte antigen DR52a, HLA-DRA/DRB3*0101, in complex with an N-terminal human platelet integrin alphaII(B)betaIII glycoprotein peptide which contains a Leu/Pro dimorphism. The 33:Leu dimorphism is the epitope for the T cell directed response in neonatal alloimmune thrombocytopenia and post-transfusion purpura in individuals with the alphaII(B)betaIII 33:Pro allele, and defines the unidirectional alloimmune response. This condition is always associated with DR52a. The crystallographic structure has been refined to 2.25 A. There are two alphabeta heterodimers to the asymmetric unit in space group P4(1)2(1)2. The molecule is characterized by two prominent hydrophobic pockets at either end of the peptide binding cleft and a deep, narrower and highly charged P4 opening underneath the beta 1 chain. Further, the peptide in the second molecule displays a sharp upward turn after pocket P9. The structure reveals the role of pockets and the distinctive basic P4 pocket, shared by DR52a and DR3, in selecting their respective binding peptide repertoire. We observe an interesting switch in a residue from the canonically assigned pocket 6 seen in prior class II structures to pocket 4. This occludes the P6 pocket helping to explain the distinctive "1-4-9" peptide binding motif. A beta57 Asp-->Val substitution abrogates the salt-bridge to alpha76 Arg and along with a hydrophobic beta37 is important in shaping the P9 pocket. DRB3*0101 and DRB1*0301 belong to an ancestral haplotype and are associated with many autoimmune diseases linked to antigen presentation, but whereas DR3 is susceptible to type 1 diabetes DR52a is not. This dichotomy is explored for clues to the disease.
J Mol Biol 2007 Aug 10
PMID:Crystallographic structure of the human leukocyte antigen DRA, DRB3*0101: models of a directional alloimmune response and autoimmunity. 1758 34

Neuroimmune interactions play a critical role in the pathogenesis of asthma. Symptoms like wheezing and cough have been attributed to neural dysregulation, whereas sensitization and the induction of allergic inflammation have been linked with the activity of dendritic cells. Neuropeptides were previously shown to control dendritic cell function in vitro, suggesting interactions between dendritic cells and sensory nerves. Here we characterized the anatomical basis of the interactions between dendritic cells and nerves in the airways of mice and monitored the changes during allergic inflammation. Airway microdissection, whole-mount immunohistology, and confocal microscopy were used for the three-dimensional quantitative mapping of airway nerves and dendritic cells along the main axial pathway of nonsensitized versus ovalbumin-sensitized and -challenged CD11c-enhanced yellow fluorescent protein (CD11c-EYFP) transgenic mice. CD11c-EYFP-positive airway mucosal dendritic cells were contacted by calcitonin gene-related peptide-immunoreactive sensory fibers and their co-localization increased in allergic inflammation. Moreover, protein gene product 9.5-positive neuroepithelial bodies and airway ganglia were associated with dendritic cells. In human airways, human leukocyte antigen DR-positive mucosal dendritic cells were found in the close proximity of sensory nerves and neuroepithelial cells. These results provide morphologic evidence of the interactions between dendritic cells and the neural network of the airways at multiple anatomical sites.
Am J Respir Cell Mol Biol 2007 Nov
PMID:Spatial interactions between dendritic cells and sensory nerves in allergic airway inflammation. 1760 Mar 12

Selection of a related or unrelated haematopoietic stem cell donor for a patient requires accurate matching of human leukocyte antigen (HLA) genes in order to maximise the beneficial effects of the transplant. There are a number of different approaches that can be made in order to achieve HLA type depending on the number of samples being processed, the level of resolution to be achieved, and the cost of providing the various tests. Each method has its advantages and disadvantages and in most laboratories, a combination of methods may be used.
Methods Mol Med 2007
PMID:An overview of HLA typing for hematopoietic stem cell transplantation. 1766 41

Minor histocompatibility (H) antigens crucially affect the outcome of human leukocyte antigen-matched allogeneic stem cell transplantation. The number of molecularly identified minor H antigens is rapidly increasing. In parallel, clinical implementation of minor H antigens for immunotherapy has gained significant interest. It is therefore timely to type stem cell transplant recipients and their donors for minor H antigens. Here, we summarize all the currently known methodologies for minor H antigen typing on the genomic and on the RNA level.
Methods Mol Med 2007
PMID:Molecular typing methods for minor histocompatibility antigens. 1766 45

An increasing number of gene polymorphisms of immune regulatory molecules are being associated with clinical performance following stem cell transplantation (SCT). These polymorphisms affect structural or regulatory changes on immune regulatory molecules including cytokines . In contrast to polymorphisms of the major histocompatibility complex, the genome variations found in these non-human leukocyte antigen genes are simple to detect, allowing studies to be done in many laboratories and transplant centres. Many forms of DNA polymorphism detection are now available, allowing even modest laboratories to mount studies of their own. Despite these advances, studies in SCT have a number of problems relating to the complex clinical situation that they study; issues of study design and data interpretation in transplant studies are complex and challenging and are the main limiting factors, which inhibit progress in confirming genetic features which influence the success of SCT.
Methods Mol Med 2007
PMID:Non-HLA gene polymorphisms in stem cell transplantation. 1766 46

Genetic risk assessment in the setting of allogeneic stem cell transplantation is one of the major goals to optimise future prophylaxis and treatment of patients: our group has focused on analysis of single-nucleotide polymorphisms (SNPs) within the intracytoplasmatic receptor NOD2/CARD15, which recognizes the bacterial cell wall compound muramyl-dipeptide and induces nuclear factor-kappaB-mediated inflammation. By performing TaqMan PCR of the three major SNPs also identified as risk factors in Crohn's disease in donors and recipients, we were able to demonstrate a major association of NOD2/CARD15 SNPs with the occurrence of severe graft-vs-host disease and resulting treatment-related mortality following human leukocyte antigen-identical sibling transplantation. Although these data need confirmation in further prospective trials, this association may not only be used for risk assessment but also point to a major pathophysiological interaction of dysregulated activation of the innate immune system and specific alloreaction.
Methods Mol Med 2007
PMID:Polymorphisms within epithelial receptors: NOD2/CARD15. 1766 47

Natural killer cells play an important role in innate immunity. They act against infected and transformed cells as part of the immune surveillance process. Their interactions with the human leukocyte antigens (HLAs) create a situation where they may act against donor hematopoietic cells following stem cell transplantation. Both killer immunoglobulin-like receptors (KIRs) and HLA types of donor and recipient are relevant in the generation of graft-vs-leukemia or graft-vs-host reactions. This chapter reviews the current knowledge on the involvement of natural killer cells in the events following hematopoietic stem cell transplantation, the structure of the genetic complex encoding the KIRs and provides a PCR-based genotyping scheme for KIR genes.
Methods Mol Med 2007
PMID:Role of natural killer cells and killer immunoglobulin-like receptor polymorphisms: association of HLA and KIRs. 1766 48

Immunity to self antigens on cancer is constrained by tolerance/ignorance. DNA vaccines encoding xenogeneic differentiation antigens, such as tyrosinase (TYR), mediate tumor protection and regression in implantable mouse models, and dogs with spontaneous melanoma. We conducted a trial of mouse and human TYR DNA vaccines in stage III/IV melanoma patients. Eighteen human leukocyte antigen (HLA)-A*0201(+) melanoma patients were randomized as follows: one group received three mouse TYR DNA injections followed by three human TYR DNA injections; the other group received the same vaccines in opposite sequence. The study was conducted at three dose levels: 100, 500, and 1,500 microg DNA/injection, administered intramuscularly (IM) every 3 weeks. Most toxicities were grade 1 injection site reactions. Seven patients developed CD8(+) T-cell responses, defined by a >3 SD increase in baseline reactivity to TYR peptide in tetramer or intracellular cytokine staining (ICS) assays. There was found to be no relationship between dose, assigned schedule, and T-cell response. At a median of 42 months follow-up, median survival has not been reached. Mouse and human TYR DNA vaccines were found safe and induced CD8(+) T-cell responses in 7 of 18 patients. T cells recognizing a native TYR peptide had a phenotype consistent with that of effector memory cells.
Mol Ther 2007 Nov
PMID:Safety and immunogenicity of tyrosinase DNA vaccines in patients with melanoma. 1772 60

Haploidentical hematopoietic stem cell transplantation (HSCT) provides an opportunity for patients to benefit from HCT when a human leukocyte antigen (HLA) genotypically matched sibling is not available. Initial results with the use of mismatched allograft has been disappointing due to the high incidence of graft-versus-host disease (GVHD) and infectious complications resulting in an unacceptable treatment-related morbidity and mortality. Recent advances with effective T-cell depletion, the use of 'megadose' of stem cells and reduced intensity conditioning has significantly decreased the early transplant related mortality and GvHD, while enabling robust and prompt engraftment, and hence enhancing the therapeutic benefits of haploidentical transplantation. However, the cardinal problems related to delayed immune reconstitution causing posttransplant infectious complications and relapse remain, limiting the efficacy of haploidentical transplant. Preliminary data have demonstrated the great potential in the use of adoptive cellular immunity and selective allodepletion in rapidly reconstituting immunity without GvHD. The encouraging reports from haploidentical transplant using noninherited maternal antigen (NIMA)-mismatched donors or natural killer alloreactive donors may greatly increase the donor availability and open a way to more appropriate donor selection in HLA-haploidentical HSCT. Future challenges remain in determining the safest approach for haploidentical transplant to be performed with minimal risk of GvHD, while preserving effective graft-versus-leukemia activity and promoting prompt immune reconstitution.
Blood Cells Mol Dis
PMID:Nonmyeloablative allogeneic hematopoietic stem cell transplant using mismatched/haploidentical donors: a review. 1788 41


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