共查询到20条相似文献,搜索用时 31 毫秒
1.
Aldemir H 《Biochemical and biophysical research communications》2008,366(2):328-334
Association with β2-microglobulin and binding a ligand are necessary conditions for cell surface expression of the antigen presenting molecules. MHC class I-related protein, MR1, is suggested to have an antigen presentation function, nevertheless the physiological ligand(s) is (are) still to be determined. In the present study, by characterising the subcellular deportment of human MR1 transfectants, we have shown its differential mobilisation. Our results demonstrated a preferential association of MR1 with β2-microglobulin in MHC class I-deficient B cell lines. Furthermore, we have evidenced diminished expression of classical MHC class I molecules in human MR1-transfected 293T cells, showing a possible interaction between MR1 and classical MHC class I molecules. 相似文献
2.
P. J. van den Elsen S. J. P. Gobin Marja C. J. A. van Eggermond A. Peijnenburg 《Immunogenetics》1998,48(3):208-221
Major histocompatibility complex (MHC) molecules serve as peptide receptors. These peptides are derived from processed cellular
or extra-cellular antigens. The MHC gene complex encodes two major classes of molecules, MHC class I and class II, whose function
is to present peptides to CD8+ (cytotoxic) and CD4+ (helper) T cells, respectively. The genes encoding both classes of MHC molecules seem to originate from a common ancestral
gene. One of the hallmarks of the MHC is its extensive polymorphism which displays locus and allele-specific characteristics
among the various MHC class I and class II genes. Because of its central role in immunosurveillance and in various disease
states, the MHC is one of the best studied genetic systems. This review addresses several aspects of MHC class I and class
II gene regulation in human and in particular, the contribution to the constitutive and cytokine-induced expression of MHC
class I and II genes of MHC class-specific regulatory elements and regulatory elements which apparently are shared by the
promoters of MHC class I and class II genes.
Received: 12 January 1998 相似文献
3.
4.
Paul J. Fairchild 《Journal of peptide science》1998,4(3):182-194
Molecules encoded by the major histocompatibility complex (MHC) are polymorphic integral membrane proteins adapted to the presentation of peptide fragments of foreign antigens to antigen-specific T-cells. The diversity of infectious agents to which an immune response must be mounted poses a unique problem for receptor–ligand interactions; how can proteins whose polymorphism is necessarily limited bind an array of peptides almost infinite in its complexity? Both MHC class I and class II determinants have achieved this goal by harnessing a limited number of peptide side chains to anchor the epitope in place while exploiting conserved features of peptide structure, independent of their primary sequence. While class I molecules interact predominantly with the N- and C-termini of peptides, class II determinants form an extensive hydrogen bonding network along the length of the peptide backbone. Such a strategy ensures high-affinity binding, while selectively exposing the unique features of each ligand for recognition by the T-cell receptor. © 1998 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
5.
Hisateru Yamaguchi Keiichiro Hashimoto 《Biochemical and biophysical research communications》2002,290(2):722-729
MR1 is a major histocompatibility complex (MHC) class I-related gene conserved among mammals, and its predicted amino acid sequence is relatively closer to the classical MHC class I molecules among several divergent class I molecules. However, as its molecular nature and function have not yet been clarified, we set out in this study to establish transfected P388 murine cell lines that stably produce a large number of MR1 proteins and conducted analyses to investigate the molecular nature of MR1. Immunoprecipitation and Western blot analyses with specific antisera revealed that the MR1 protein can associate with beta(2)-microglobulin, suggesting its molecular form of a typical class I heterodimer composed of a heavy and a light chain (beta(2)-microglobulin), like the classical MHC class I molecules. 相似文献
6.
Sung-tae Yee Yoshiaki Okada Kazumasa Ogasawara Satoshi Omura Akira Takatsuki Terutaka Kakiuchi Daisaku Muno Eiki Kominami Toshiaki Mizuochi 《Microbiology and immunology》1997,41(7):563-570
Peptides derived from endogenous proteins are presented by MHC class I molecules, whereas those derived from exogenous proteins are presented by MHC class II molecules. This strict segregation has been reconsidered in recent reports in which exogenous antigens are shown to be presented by MHC class I molecules in the phagocytic pathway. In this report, the presentation pathway of an exogenously added highly antigenic polypeptide encoded by the murine AIDS (MAIDS) defective virus gag p12 gene is investigated. A 25-mer polypeptide (P12–25) encoded within the gag p12 region of the MAIDS defective virus was found to be effective in stimulating unprimed B6 (H-2b) CD8+ T cells in vitro. The presentation of P12–25 is sensitive to cytochalasin B and D, brefeldin A and gelonin, a ribosome-inactivating protein synthesis inhibitor, but less sensitive or resistant to lactacystin, a highly specific inhibitor of the proteasome. Interestingly, CA-074, a selective inhibitor of cathepsin B, inhibited presentation of the polypeptide, indicating its involvement in the degradation of the P12–25 polypeptide. In fact, when P12–25 was digested with purified cathepsin B in vitro, a highly antigenic 11-mer peptide containing the class I (H-2Db)-binding motif was obtained. Our results favor the phagosome/macropinosome-to-cytosol-to-endoplasmic reticulum (ER)-to-cell surface pathway for exogenous antigens presented by MHC class I molecules. These findings may be relevant to exploiting peptide vaccines that specifically elicit CD8+ T cell immunity in vivo. 相似文献
7.
8.
P. A. Steerenberg W. H. De Jong E. Geerse A. De Graaf R. J. Scheper W. Den Otter E. J. Ruitenberg 《Cancer immunology, immunotherapy : CII》1991,33(3):189-197
Summary We investigated the cellular composition and the major histocompatibility complex (MHC) class II antigen expression in the draining lymph node and the tumour during potentiation of the immune response by intralesional bacillus Calmette-Guérin (BCG) administration in the line 10 hepatocellular carcinoma in the strain 2 guinea-pig. Five days after its injection BCG induced a ninefold increase in the number of draining lymph node cells and an increased MHC class II expression. This increased MHC class II expression was mostly due to the selective increase of B cells in the lymph nodes, and to a lesser extent to the increase of T cells expressing MHC class II antigens. Taking into account this nine-fold increase, intralesional treatment of BCG increased considerably the number of T helper/inducer (anti-CT7) and T suppressor/cytotoxic (anti-CT6) lymph node cells expressing MHC class II antigen. The percentage of tumourinfiltrating T cells expressing MHC class II antigen in the tumour was higher than the percentage of T cells in the regional draining lymph node of non-treated guinea-pigs, indicating the presence of activated T cells in the tumour. After treatment with BCG no further increase in MHC class II expression was measured in the tumour, nor was any phenotypical change of the tumour-infiltrating T cells found. In conclusion, with the use of two-colour flow cytofluorometry we have shown that the potentiation of the already existing immune response to line 10 is accompanied by a considerable increase in T helper/inducer, T suppressor/cytotoxic cells and MHC class II antigen in the regional lymph node. Whether this is essential for the potentiation of the immune response causing tumour regression and long-lasting immunity is a subject for further study. 相似文献
9.
Purpose The efficient identification of peptide antigens recognized by ovarian cancer-specific cytotoxic T lymphocytes (CTL) requires
the use of well-characterized ovarian cancer cell lines. To develop such a panel of cell lines, 11 ovarian cancer cell lines
were characterized for the expression of class I and class II major histocompatibility complex (MHC)-encoded molecules, 15
tumor antigens, and immunosuppressive cytokines [transforming growth factor β (TGF-β) and IL-10].
Methods Class I MHC gene expression was determined by polymerase chain reaction (PCR), and class I and class II MHC protein expression
was determined by flow cytometry. Tumor antigen expression was determined by a combination of polymerase chain reaction (PCR)
and flow cytometry. Cytokine expression was determined by ELISA.
Results Each of the ovarian cancer cell lines expresses cytokeratins, although each cell line does not express the same cytokeratins.
One of the lines expresses CD90, which is associated with a fibroblast lineage. Each of the cell lines expresses low to moderate
amounts of class I MHC molecules, and several of them express low to moderate amounts of class II MHC molecules. Using a combination
of PCR and flow cytometry, it was determined that each cell line expressed between six and thirteen of fifteen antigens tested.
Little to no TGF-β3 was produced by any of the cell lines, TGF-β1 was produced by three of the cell lines, TGF-β2 was produced
by all of the cell lines, with four of the cell lines producing large amounts of the latent form of the molecule, and IL-10
was produced by one of the cell lines.
Conclusions Each of the 11 ovarian cancer lines is characterized by a unique expression pattern of epithelial/fibroblast markers, MHC
molecules, tumor antigens, and immunosuppressive cytokines. Knowledge of these unique expression patterns will increase the
usefulness of these cell lines in identifying the antigens recognized by ovarian cancer-specific CTL. 相似文献
10.
Regulation of B lymphocyte proliferation is critical to maintenance of self-tolerance, and intercellular interactions are likely to signal such regulation. Here, we show that coligation of either the adhesion molecule ICAM-1/CD54 or MHC II with CD40 inhibited cell cycle progression and promoted apoptosis of mouse splenic B cells. This resulted from specific blockade of NF-kappa B induction, which normally inhibits apoptosis. LPS- or B cell receptor (BCR)-induced proliferation was not inhibited by these treatments, and mAb-induced association of CD40 with other B cell surface molecules did not have these effects. Addition of BCR or IL-4 signals did not overcome the effect of ICAM-1 or MHC II on CD40-induced proliferation. FasL expression was not detected in B cell populations. These results show that MHC II and ICAM-1 specifically modulate CD40-mediated signaling, so inhibiting proliferation and preventing inhibition of apoptosis. 相似文献
11.
12.
Major histocompatibility complex class II (MHC II) molecules are targeted to endocytic compartments, known as MIIC, by the invariant chain (Ii) that is degraded upon arrival in these compartments. MHC II acquire antigenic fragments from endocytosed proteins for presentation at the cell surface. In a unique and complex series of reactions, MHC II succeed in exchanging a remaining fragment of Ii for other protein fragments in subdomains of MIIC before transport to the cell surface. Here, the mechanisms regulating loading and intracellular trafficking of MHC II are discussed. 相似文献
13.
MHC class II compartments in human dendritic cells undergo profound structural changes upon activation 总被引:2,自引:0,他引:2
Barois N de Saint-Vis B Lebecque S Geuze HJ Kleijmeer MJ 《Traffic (Copenhagen, Denmark)》2002,3(12):894-905
Immature dendritic cells efficiently capture exogenous antigens in peripheral tissues. In an inflammatory environment, dendritic cells are activated and become highly competent antigen-presenting cells. Upon activation, they lose their ability for efficient endocytosis and gain capability to migrate to secondary lymphoid organs. In addition, peptide loading of MHC class II molecules is enhanced and MHC class II/peptide complexes are redistributed from an intracellular location to the plasma membrane. Using immuno-electron microscopy, we show that activation of human monocyte-derived dendritic cells induced striking modifications of the lysosomal multilaminar MHC class II compartments (MIICs), whereby electron-dense tubules and vesicles emerged from these compartments. Importantly, we observed that MHC class II expression in these tubules/vesicles transiently increased, while multilaminar MIICs showed a strongly reduced labeling of MHC class II molecules. This suggests that formation of the tubules/vesicles from multilaminar MIICs could be linked to transport of MHC class II from these compartments to the cell surface. Further characterization of endocytic organelles with lysosomal marker proteins, such as the novel dendritic cell-specific lysosomal protein DC-LAMP, HLA-DM and CD68, revealed differential sorting of these markers to the tubules and vesicles . 相似文献
14.
Antigen loading of MHC class I molecules in the endocytic tract 总被引:4,自引:1,他引:3
Kleijmeer MJ Escola JM UytdeHaag FG Jakobson E Griffith JM Osterhaus AD Stoorvogel W Melief CJ Rabouille C Geuze HJ 《Traffic (Copenhagen, Denmark)》2001,2(2):124-137
Major histocompatibility complex (MHC) class I molecules bind antigenic peptides that are translocated from the cytosol into the endoplasmic reticulum by the transporter associated with antigen processing. MHC class I loading independent of this transporter also exists and involves peptides derived from exogenously acquired antigens. Thus far, a detailed characterization of the intracellular compartments involved in this pathway is lacking. In the present study, we have used the model system in which peptides derived from measles virus protein F are presented to cytotoxic T cells by B-lymphoblastoid cells that lack the peptide transporter. Inhibition of T cell activation by the lysosomotropic drug ammoniumchloride indicated that endocytic compartments were involved in the class I presentation of this antigen. Using immunoelectron microscopy, we demonstrate that class I molecules and virus protein F co-localized in multivesicular endosomes and lysosomes. Surprisingly, these compartments expressed high levels of class II molecules, and further characterization identified them as MHC class II compartments. In addition, we show that class I molecules co-localized with class II molecules on purified exosomes, the internal vesicles of multivesicular endosomes that are secreted upon fusion of these endosomes with the plasma membrane. Finally, dendritic cells, crucial for the induction of primary immune responses, also displayed class I in endosomes and on exosomes. 相似文献
15.
Keiko Naitoh Yasuhisa Ichigi Kensuke Miyake Atsushi Muraguchi Masao Kimoto 《Microbiology and immunology》1994,38(12):967-976
The function of MHC class II HLA-DR molecules expressed on a human B lymphoid progenitor cell line FL8.2.4.4 (abbreviated as FL4.4) was examined. FL4.4 cells expressed HLA-DR molecules and stimulation of the DR molecules by anti-DR mAb or by superantigen TSST-1 induced strong augmentation of homocytic aggregation and protein tyrosine phosphorylation in FL4.4 cells. Induced homocytic aggregation in FL4.4 consists both of LFA-1/ICAM-1-dependent and -independent pathways as revealed by mAb blocking experiments. Metabolic inhibitors, NaN3 and cytochalasin B, blocked the induced homocytic aggregation of FL4.4. Early mature Daudi B cell lines also showed a similar type of homocytic aggregation by stimulation with anti-DR mAb. Daudi cells are more sensitive to protein kinase inhibitors herbimycin A and H7 than FL4.4 cells in their blocking of induced homocytic aggregation, while W7 showed stronger inhibitory effects on FL4.4 cells than on Daudi cells. Western blotting analysis revealed that the stimulation of DR molecules induced protein tyrosine phosphorylation of 100-kDa, 90-kDa, 60-kDa and 55-kDa proteins in FL4.4 cells, while, in Daudi cells 110-kDa, 100-kDa and 80-kDa proteins were phosphorylated. These results suggest that different signaling pathways through class II molecules are employed depending on the maturational stage of B-cell differentiation. 相似文献
16.
Straten Pt Dahl C Schrama D Pedersen LØ Andersen MH Seremet T Bröcker EB Guldberg P Becker JC 《Cancer immunology, immunotherapy : CII》2006,55(5):495-502
It is generally believed that priming of efficient T-cell responses takes place in peripheral lymphoid tissues. Although this notion has been rigidly proven for infectious diseases, direct evidence for lymph node priming of in vivo T-cell responses against tumors is still lacking. In the present study, we conducted a full and nonbiased comparison of T-cell clonotypes in melanoma lesions and corresponding sentinel lymph nodes. Whereas most tumor lesions comprised a high number of T-cell clonotypes, only a small number of clonally expanded T cells were detected in the draining lymph nodes. Comparative clonotype mapping demonstrated the presence of identical T-cell clonotypes in the tumors and the respective sentinel lymph nodes, only when tumor cells were present in the latter. However, taking advantage of clonotype specific PCR amplification, TCR sequences representing clonally expanded T cells at the tumor site could be detected in the lymph nodes draining the tumors even in the absence of tumor cells. Evidence for the tumor-specific characteristics of these cells was obtained by in situ staining with peptide/HLA class I complexes demonstrating the presence of MART-1/HLA-A2- and MAGE-3/HLA-A2-reactive T cells at the tumor site, as well as in the draining lymph node. Our data indicate that T-cell responses to melanoma are primed in the sentinel lymph node by cross presentation of tumor antigens by dendritic cells. 相似文献
17.
18.
Doytchinova I Petkov P Dimitrov I Atanasova M Flower DR 《Protein science : a publication of the Protein Society》2011,20(11):1918-1928
Major histocompatibility complex (MHC) II proteins bind peptide fragments derived from pathogen antigens and present them at the cell surface for recognition by T cells. MHC proteins are divided into Class I and Class II. Human MHC Class II alleles are grouped into three loci: HLA-DP, HLA-DQ, and HLA-DR. They are involved in many autoimmune diseases. In contrast to HLA-DR and HLA-DQ proteins, the X-ray structure of the HLA-DP2 protein has been solved quite recently. In this study, we have used structure-based molecular dynamics simulation to derive a tool for rapid and accurate virtual screening for the prediction of HLA-DP2-peptide binding. A combinatorial library of 247 peptides was built using the "single amino acid substitution" approach and docked into the HLA-DP2 binding site. The complexes were simulated for 1 ns and the short range interaction energies (Lennard-Jones and Coulumb) were used as binding scores after normalization. The normalized values were collected into quantitative matrices (QMs) and their predictive abilities were validated on a large external test set. The validation shows that the best performing QM consisted of Lennard-Jones energies normalized over all positions for anchor residues only plus cross terms between anchor-residues. 相似文献
19.
Yong Chen Feng Gao Fuliang Chu Hao Peng Yiwei Liu George F. Gao 《Journal of molecular biology》2009,386(3):841-18025
The leukocyte Ig-like receptor (LILR/ILT/LIR) family comprises 13 members that are either activating or inhibitory receptors, regulating a broad range of cells in the immune responses. LILRB1 (ILT2), LILRB2 (ILT4) and LILRA1 (LIR6) can recognize MHC (major histocompatibility complex) class I or class I-like molecules, and LILRB1/HLA-A2, LILRB1/UL18 and LILRB2/HLA-G complex (extracellular domains D1D2) structures have been solved recently. The details of binding to MHC have been described. Despite high levels of sequence similarity among LILRA1, LILRA2 (ILT1), LILRA3 (ILT6) and LILRB1/B2, all earlier experiments showed that LILRA2 does not bind to MHC, but the reason is unknown. Here, we report the LILRA2 extracellular D1D2 domain crystal structure at 2.6 Å resolution, which reveals structural shifts of the corresponding MHC-binding amino acid residues in comparison with LILR B1/B2, explaining its non-binding to MHC molecules. We identify some key residues with great influence on the local structure, which exist only in the MHC-binding receptors. Moreover, we show that LILRA2 forms a domain-swapped dimer. Further work with these key swapping residues yields a monomeric form, confirming that the domain-swapping is primarily amino acid sequence-specific. The structure described here supports the dimer conformation in solution observed earlier, and implies a stress-induced regulation by dimerization, consistent with its function as a heat shock promoter. 相似文献
20.
This study was aimed at creating a more effective tumor cell vaccine by suppressing Ii protein in the presence of MHC class
II molecules within a cancer cell. Absence of the Ii protein, which normally blocks the antigenic-peptide-binding site of
MHC class II molecules at synthesis in the endoplasmic reticulum, presumably increases the range of cancer-related epitopes
presented to CD4+ helper T cells. Effective suppression of Ii protein was achieved with an antisense, phosphorothioate oligonucleotide, which
was selected on the basis of (1) the RNase H activation assay, (2) an assay for Ii protein suppression, and (3) a test for
potency with respect to the extent of base sequence (“sequence walking”). The SaI murine sarcoma, which is MHC-class-I+ and MHC-class-II−, Ii-protein−, upon transfection with genes for either interferon γ or the MHC class II transactivator, came to express MHC class II molecules
and Ii protein. In each line of transfected tumor cells, the antisense oligonucleotide profoundly suppressed Ii protein in
35%–55% cells, without affecting expression of MHC class II molecules. Inoculation of mice with such Ii-protein-suppressed
tumor vaccine cells, after either formaldehyde fixation or X-irradiation, led to much greater protection against challenge
with the parental SaI sarcoma than did inoculation with untreated cells. This approach to cancer cell vaccination can be applied
in a wide range of human tumors.
Received: 22 June 1999 / Accepted: 28 July 1999 相似文献