CIITA反义RNA抑制MHCII类分子表达

为探索利用CIITA (MHCclassIItransactivator)基因反义RNA抑制MHCII类分子表达的可能性 ,为CIITA的应用研究奠定基础。利用RT PCR扩增能与CIITAcDNA第 95至 5 0 0bp互补的片段 ,并构建成pcDNA3/CIITAa 重组质粒 ,脂质体转染法将其转入人HeLa/Raji细胞和猪PIEC/L2 3细胞 ,流式细胞术动态检测反义RNA对人 /猪MHCII类分子的抑制率和抑制程度。结果显示HeLa、Raji、PIEC和L2 3四种细胞MHCII类分子受抑制率分别为 4 6 7% ( 7/ 15 ) ,4 0 % ( 6 / 15 ) ,4 6 7% ( 7/ 15 )和33 3% ( 5 / 15 )。典型受抑克隆细胞MHCII类分子受抑程度高达 85 % ,反义RNA对MHCII类分子的抑制时间持续 35～ 5 0d。CIITA反义RNA能有效抑制人 /猪MHCII类分子的表达 ,它在自身免疫和移植免疫中有一定的应用前景     

Uterine NK Cells and Trophoblast HLA Class I Molecules

PROBLEM: To investigate the proposal that NK cells in decidua may control trophoblast migration during implantation of the human placenta. METHOD: Use Mab specific for HLA-G and for HLA-C in association with flow cytometry and immunoprecipitation to determine the expression of these HLA molecules by trophoblast. Expression of Killer inhibitory/activatory receptors (KIR/KAR) and the CD94 receptor by decidual NK cells was also studied. RESULTS: Extravillous trophoblast expressed HLA-G and HLA-C in both β₂m-associated form and as free heavy chains. KIR and KAR are expressed by decidual NK cells. The repertoire of receptors varied between different women and also between blood and decidual NK cells from the same women. The expression of CD94 was also different between blood and decidual NK cells. CONCLUSION: The recognition of HLA-G/HLA-C by KIR/KAR and CD94 could provide a mechansm by which decidual NK cells control trophoblast migration.     

MHC Class II epitope predictive algorithms

Major histocompatibility complex class II (MHC‐II) molecules sample peptides from the extracellular space, allowing the immune system to detect the presence of foreign microbes from this compartment. To be able to predict the immune response to given pathogens, a number of methods have been developed to predict peptide–MHC binding. However, few methods other than the pioneering TEPITOPE/ProPred method have been developed for MHC‐II. Despite recent progress in method development, the predictive performance for MHC‐II remains significantly lower than what can be obtained for MHC‐I. One reason for this is that the MHC‐II molecule is open at both ends allowing binding of peptides extending out of the groove. The binding core of MHC‐II‐bound peptides is therefore not known a priori and the binding motif is hence not readily discernible. Recent progress has been obtained by including the flanking residues in the predictions. All attempts to make ab initio predictions based on protein structure have failed to reach predictive performances similar to those that can be obtained by data‐driven methods. Thousands of different MHC‐II alleles exist in humans. Recently developed pan‐specific methods have been able to make reasonably accurate predictions for alleles that were not included in the training data. These methods can be used to define supertypes (clusters) of MHC‐II alleles where alleles within each supertype have similar binding specificities. Furthermore, the pan‐specific methods have been used to make a graphical atlas such as the MHCMotifviewer, which allows for visual comparison of specificities of different alleles.     

T Cells are Unresponsive to Transgenic MHC Class II Molecules Expressed on Pancreatic β Cells

It has been proposed that the autoimmune attack on the pancreatic β cells leading to insulin-dependent diabetes mellitus can be caused by the expression of MHC class II molecules on the β cells. Transgenic mice expressing normal levels of allogeneic MHC class II A^k on the β-cell surface (IP-A^k) do not develop either insulitis or diabetes, yet these mice are not tolerant to A^k when expressed on normal antigen-presenting cells. The authors have stimulated T cells from IP-A^k mice in vitro with A^k-expressing β cells. Mice were also primed in vivo in order to facilitate the antiallogeneic response. The authors found that neither IP-A^k positive nor IP-A^k negative mice were able to respond to A^k-expressing β cells, and that in vivo priming does not overcome this inability. They suggest that β cells do not act as antigen-presenting cells, probably due to inability of delivering costimulatory signals. This strengthens the notion that MHC class II expression per se is not sufficient to induce an autoimmune attack on the β cells.     

MHCII类反式激活蛋白调控肿瘤细胞HLA分子的表达

为研究肿瘤细胞MHCII类分子表达及对IFN γ诱导HLA分子表达的反应性与CIITA表达的关系 ,本文采用Westernblot、免疫组化和流式细胞术检测肿瘤细胞HLA分子表达 ,以RT PCR检测肿瘤细胞CIITA基因表达。肿瘤细胞HLAII类分子表达与CIITA表达一致 ;组成性或诱导性表达CIITA的肿瘤细胞 ,经IFN γ作用后其HLAI、II类分子表达增高 ;IFN γ诱导后仍不表达CIITA的肿瘤细胞 ,其对IFN γ促HLA表达的作用不反应。提示 ,某些肿瘤细胞对IFN γ不能诱导HLA分子表达与CIITA诱导性表达缺陷有关。表面CIITA参与调控肿瘤细胞HLAI、II类分子表达。     

Immunohistochemical Characterization and Localization of MHC Class II Antigen-Presenting Cells in the Periodontal Ligament of Rat Incisors

Dendritic cells have been identified both in lymphoid and nonlymphoid tissues as non-phagocytic antigen-presenting cells, equipped with extensive flamelike cytoplasmic projections. Our immunohistochemical study revealed presence of a large population of dendritic cells and other immunocompetent cells, showing a region-specific distribution, in the lingual periodontal ligament of continuously erupting rat incisors. This study aims to reveal the kinetics and cytological characterization of immunocompetent cells in the periodontal ligament of rat incisors with special reference to their differentiation pathway in the unique local environment.     

Class II MHC peptide loading by the professionals

The loading of class II MHC molecules with antigenic peptides is largely confined to the endocytic vesicles of specialized antigen-presenting cells (APCs), such as B cells, macrophages and dendritic cells. At first glance, the pathway utilized by each of these professional APCs to generate class II-peptide complexes on their surface appears to be indistinguishable. All three types of APC rely on the chaperone Ii for correct class II assembly and transport to the endocytic pathway, they all depend on the action of specific cysteine proteases to remove Ii from the class II-Ii complex, and they all utilize the class II-like molecule DM to facilitate peptide loading. A closer look, however, reveals subtle yet important differences in the class II maturation pathway between each of these APCs, which befit the unique roles these individual cells play in eliciting CD4(+) T-cell responses.     

Identification of autoantigen epitopes in MHC Class II transgenic mice

Summary: The major histocompatibility (MHC) class Ib molecules HLA-E, HIA-F and HLA-G are relatively non-polymorphic compared to class la molecules. Both HLA-E and HLA-G bind peptides and are involved in natural killer (NK)-cell recognition, but the role of HLA-F is unclear. HLA-E binds specifically to the conserved leader sequence peptides from the class la MHC molecules and interacts on the cell surface with the CD94/NKG2 class of NK-cell receptors. The framework structure of HLA-E is similar to that of the MHC class la molecules, but the peptide-binding groove is highly adapted for the specific binding of the leader sequence peptides. This is different from class la molecules, which have highly promiscuous peptide-binding grooves. The HLA-E groove makes full use of all the available pockets and imposes specificity along the entire length of the peptide. HLA-G binds nonamer peptides with leucine or isoleucine at position 2, proline at position 3 and leucine at position 9. Expression of HLA-G inhibits NK cells expressing the CD94/NKG2 class of receptors, though an interaction with these receptors has not been directly demonstrated.     

Presence of CD4+ and CD8+ T Cells and Expression of MHC Class I and MHC Class II Antigen in Horses with Borna Disease Virus-Induced Encephalitis

Tissues from 9 horses and 1 donkey suffering from natural Borna disease were investigated immunomorphologically. Lymphocytic inflammatory reactions and increased expressions of MHC class I and class II antigen were found in the brain as well as in the trigeminal and olfactory system. Perivascular inflammatory infiltrates were dominated by CD4+ T cells, whereas the majority of CD8+ T cells were disseminated intraparenchymally. No evidence of inflammation was found in the retina. Borna disease virus proteins and nucleic acids were present in the hippocampus, thalamus and medulla oblongata in all 10 animals, in the cerebral cortex, retina, trigeminal ganglion and nerve in 9, in the olfactory epithelium in 6 and in roots and proximal parts of large peripheral nerves in 3. No evidence of infection was found in the autonomic nervous system, lung, heart, liver, kidney or gut. BDV- proteins and nucleic acids were even more abundant in the trigeminal system than in the olfactory system, suggesting that infection may have occured via the trigeminal nerve.     

T-Cell Proliferation and Expression of MHC Class II Antigens

Two monoclonal antibodies to major histocompatibility complex (MHC) class II antigens, which in combination identify β chains encoded by the SB and DR loci, were used to investigate which of these gene- products were expressed at the cell surface of unstimulated T cells and at various stages of mitogen-induced T-cell maturation. In tests on blood lymphocytes from healthy donors 12% of Tcells expressed class II antigens, but only SB antigens were expressed. During activation of T lymphocytes, SB-coded antigens were expressed before DR antigens, and the kinetics of SB expression correlated with the proliferative response of T cells. These results and consideration of recent reports from other laboratories lead us to suggest that 58-coded class II antigens play a role in T-cell proliferation.     

Expression of MHC Class II Antigens During Xenopus Development

Larval and adult forms of the amphibian Xenopus differ in their MHC class II .expression. In tadpoles, class II epitopes can be detected by monoclonal antibodies only on B cells, macrophages (whatever their location), spleen reticulum, thymus epithelium, and the pharyngobuccal cavity. In contrast, all adult T cells express class II on their surface. The transitions in class II expression occur at metamorphosis and are accompanied by other changes. The skin is invaded by class II positive dendritic cells, and the skin glands differentiate and also express class II. The gut, which expressed class II in discrete areas of the embryonic tissue, becomes invaded with B cells, and its epithelium also becomes class II positive.     

Disparate Role of LIGHT in Organ-specific Donor T Cells Activation and Effector Molecules in MHC Class II Disparate GVHD

Background  

The present studies determined the role of LIGHT on organ-specific cytokine and effector molecules in acute graft-versus-host disease.