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CD59 is a recently discovered complement (C) regulatory protein. Three activities of CD59 have been recognized so far. It can downregulate the activation of the C cascade at membrane attack complex formation stage, it participates in T-cell rosette formation with erythrocytes and appears to be necessary for T-cell activation. CD59 is broadly distributed on cells of various organs and this is compatible with its function of protecting cells and tissues from incidentally activated autologous C. CD59 is encoded by a single gene residing on chromosome 11. The entire sequence of CD59 cDNA is known, from which the amino acid structure of CD59 has been deduced. Mature CD59 is made up of 103 amino acids. It has two potential N-glycosylation sites. Carbohydrate constitutes about 20% of the molecular mass of CD59. The protein part of the molecule is covalently linked to an oligosaccharide which, in turn, is glycosydically linked to phosphatidylinositol (PI). CD59 is anchored to the cells via PI moiety. The fine structure of the PI anchor of CD59 has not yet been established. Decreased expression of CD59 has been shown in two diseases. In paroxysmal nocturnal hemoglobinuria, erythrocytes (type III) lacking CD59 (and other PI proteins) have susceptibility to lysis by membrane attack complex. In psoriasis, expression of CD59 (and CD55) is drastically decreased in psoriatic lesions, presumably due to PI cleavage involving signal transduction mechanism(s) leading to increased proliferation of various cell types in lesional skin. 相似文献
3.
D. Y. Mason W. M. Comans-Bitter J. L. Cordell M. A. Verhoeven J. J. van Dongen 《The American journal of pathology》1990,136(6):1215-1222
Monoclonal antibody L26 is a highly selective marker of B cells and B-cell neoplasms in paraffin-embedded tissues, but it suffers from the drawback that the target molecule has not been identified. In this paper we provide evidence by two independent techniques that antibody L26 recognizes an intracellular epitope on the CD20 antigen (a pan B-cell marker). When this antigen was redistributed on the surface of unfixed viable B cells by incubation with monoclonal anti-CD20 followed by anti-mouse Ig, the diffuse cytoplasmic staining of L26 was abolished and replaced by coincident dotlike labeling for antibody L26 and the CD20 antigen. None of the other antibodies tested (covering 10 different B-cell-associated antigens) had this effect on the L26 staining pattern. Furthermore, COS-1 cells transfected with cDNA encoding the CD20 molecule gave positive staining with antibody L26 and with two other CD20 reagents, but not with antibodies to other pan B-cell markers (eg, CD19 and CD22). 相似文献
4.
S. FUJII K. ONO A. TAKEUCHI T. AKI S. SHIGETA O. SUZUKI T. JYO U. YAMASHITA† 《Clinical and experimental allergy》1997,27(9):1086-1094
Background T-cell epitopes on Der 1 and Der 2 groups, the major mite allergens, have been intensively analysed, while those on the other important allergens remain to be elucidated. We have cloned four cDNAs coding for important mite allergens on the basis of frequency and capacity of IgE binding. Stimulatory action of glutathione S-transferase-fused Mag1 on lymphocytes from mite-allergic patients was relatively high among them. Objective To identify T-cell epitopes on Mag1, we studied the stimulating activity of truncated Mag1 proteins and synthetic peptides on proliferative response of lymphocytes from mite antigen-immunized mice and mite-sensitive patients. Methods Truncated Mag1 proteins were expressed as a fusion protein with β-galactosidase in Escherichia coli pop2136 carrying a variety of deleted Mag1 inserts. Murine T-cell epitope regions were estimated by the truncated antigen-induced lymphocyte proliferation assay. Overlapping peptides covering the whole sequence of the presumed T-cell epitope regions were synthesized to identify the epitope core. sequences using murine and human Mag1-specific T-cell lines. Results Amino acid range 56–70 on Mag1 molecule showed remarkable stimulatory action on murine T cells, while amino acid ranges 51–65 and 86–100 had potent stimulatory activity on human T cells. Conclusion These results suggest that Mag1 is a valuable antigen suitable for studies on T-cell responses and T-cell epitopes in mice and humans. 相似文献
5.
CD59 defines an N-glycosylated glycoprotein expressed on various hemopoietic cells. It is anchored to the cell membrane by a glycosylpbospbatidylinositol linkage and restricts the action of homologous complement. Monoclonal antibodies 2/24, 182, Fib75.1, BRIC 229, MEM-43, and YTH 53.1 were compared by immunoblotting against normal erythrocyte ghosts. All six stained a diffuse band of 17-25 kDa, but BRIC 229 also detected bands at 35 and 80 kDa. 2/24 reacts with all red blood cells (RBCs) tested, including Rhnull; Ob; ii; Ko; FY:-1,-2,-3; JK:-1,-2,-3; S-s-U-; p; CO:-1,-2; Yt(a-); Jr(a-); Vel-; At(a-); Cr(a-); GE:-2,-3; Wr(a+b+ MkMk; Jo(a-); and Lan-. 2-aminoethylisotbiouronium bromide treatment of erythrocytes destroyed blotting and serologic reactivity of all six antibodies. Pronase treatment reduced serologic reactivity and blotting ability of all antibodies except BRlC 229. Reactivity of all six antibodies was reduced with RBCs from paroxysmal nocturnal hemoglobinuria patients. Flow cytometric analysis was used to demonstrate that 182, Fib75.1, BRIC 229, YTH 53.1, and MEM-43 competitively inhibited the binding of 2/24 to RBCs, thus demonstrating that all six antibodies detect epitopes on the same molecule. 相似文献
6.
R A Brooimans A A Van der Ark M Tomita L A Van Es M R Daha 《European journal of immunology》1992,22(3):791-797
CD59 is a 18-20-kDa membrane glycoprotein that inhibits formation of the membrane attack complex of complement (C) on homologous cells. In the present study we analyzed the expression and function of CD59 on human endothelial cells. Immunohistochemical analysis of renal cortex demonstrated a predominant expression of CD59 on peritubular capillary endothelial cells and glomerular endothelial cells. Flow cytometry analysis showed that human umbilical vein endothelial cells (HUVEC) expressed CD59 and the fluorescence intensity was approximately four times that of peripheral blood lymphocytes. CD59 is detected on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a single 20-kDa molecule in 2% deoxycholate extracts of HUVEC. CD59 was released from the surface of HUVEC by phosphatidylinositol-specific phospholipase C, demonstrating that it is attached to the cell membrane by means of a glycolipid anchor. The functional activity of CD59 expressed on HUVEC was studied. Blocking of CD59 antigen with F(ab')2 fragments of polyclonal anti-CD59 enhanced markedly the susceptibility of HUVEC to C-mediated lysis. This effect was dependent on the amount of blocking antibodies added. Northern blot analysis revealed the presence of three species of mRNA expressed in HUVEC, which hybridized to a cDNA probe specific for CD59, with sizes of about 800, 1400 and 2000 bp. These findings suggest that CD59 may be important in protection of endothelial cells against C-mediated damage at local sites of inflammation, thereby maintaining the vascular integrity in vivo. 相似文献
7.
CD59 molecule: a second ligand for CD2 in T cell adhesion. 总被引:14,自引:0,他引:14
M Deckert J Kubar D Zoccola G Bernard-Pomier P Angelisova V Horejsi A Bernard 《European journal of immunology》1992,22(11):2943-2947
The T cell surface molecule CD2 forms, with its counter-receptor CD58 (LFA-3), a powerful adhesion/activation pathway. There is some evidence that CD2 might bind more than a single ligand. Chinese hamster ovary cells (CHO) expressing human CD59 after cDNA transfection (CD59+CHO) form rosettes with human T cells; these rosettes are inhibited in a dose-dependent fashion by the CD59 monoclonal antibody (mAb) H19 and by the CD2 mAb O275 known to block natural rosettes, but not by the CD2R mAb D66, a poor rosette blocker. CD2+CHO transfectants form rosettes with human erythrocytes; these rosettes are inhibited by the CD59 mAb H19 in addition to CD2 mAb O275 and CD58 mAb; murine thymoma cells expressing human CD2 form rosettes with CD59+CHO cells that again are blocked by CD59 H19 and by CD2 O275 mAb. In a marked contrast with H19, two others CD59 mAb, YTH 53.1 and MEM 43, which react with a different epitope on CD59, led to a 50%-70% increase of the number of cells forming rosettes. In addition to rosette experiments, the binding of 125I-labeled CD59 molecules to CD2+CHO cells was specifically inhibited by unlabeled CD59 molecule and CD2 mAb. Furthermore, the binding of CD59 molecules to resting T cells induced expression of CD2R epitopes. These results directly show that CD2 binds CD59 and that subtle molecular changes occur upon binding. 相似文献
8.
The T11(3) epitope of the CD2 molecule, sheep erythrocytes, and the alternative T-cell activation pathway. 总被引:1,自引:0,他引:1
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In this study, results are presented showing that the T11(3) epitope of the CD2 molecule is expressed on unfractionated peripheral blood mononuclear cells, resting T cells and activated T cells. T11(3) is not therefore, an activation-specific CD2 epitope. Sheep erythrocytes (SRC) which present a cell-surface ligand for CD2 could not effectively replace anti-T11(2) in initiating proliferation of resting T cells, stimulated by anti-T11(3). SRC with either of these anti-CD2 monoclonal antibodies did activate resting T cells, but proliferation required the presence of added IL-2. 相似文献
9.
Characterization of the common acute lymphoblastic leukaemia antigen (CD10) as an activation molecule on mature human B cells. 总被引:2,自引:0,他引:2
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N Kiyokawa Y Kokai K Ishimoto H Fujita J Fujimoto J I Hata 《Clinical and experimental immunology》1990,79(3):322-327
Distinct expression pattern of CD10 molecules during B cell activation was analysed using in vivo and in vitro systems. By two-colour flowcytometrical analysis, CD10 was found to be expressed at a specific stage of in vivo activating B cells. The expression of CD10 during B cell activation appeared to be unique from that of other activation-related B cell antigens including L29, MA6, OKT9 and OKT10. Although the expression of CD10 was associated with that of the activation-related B cell antigens, CD10+ B cells could be separated in the distinct fractions to those expressing other activation-related B cell antigens when fractionated by cell gravity. In particular, certain CD10+ B cells were detected positive for the resting B cell antigen, L30. In vitro studies revealed that CD10+ B cells arose from CD10- B cells at an early step of B cell activation, and disappeared lately when activated by Staphylococcus aureus Cowan I. Collectively, CD10 was an antigen transiently expressed at an early phase of B cell activation process. Expression of CD10 and other antigens on Burkitt's lymphomas (15 cases) was studied next. All cases were CD10+, and 87% (13 cases) were also L30+. In addition, six of CD10+ L30+ cases were L29+. This observation suggested that Burkitt's lymphomas were phenotypically similar to the B cells at an early phase of activation, those expressing CD10 and L30, simultaneously. The present study has dissected a precise expression pattern of CD10 on mature B cell activation in vitro and in vivo, and could be implicated for the histogenesis of one of the poorly characterized B cell lymphoma, namely Burkitt's lymphoma. 相似文献
10.
Identification of the CD85 antigen as ILT2, an inhibitory MHC class I receptor of the immunoglobulin superfamily. 总被引:4,自引:0,他引:4
A H Banham M Colonna M Cella K J Micklem K Pulford A C Willis D Y Mason 《Journal of leukocyte biology》1999,65(6):841-845
The CD85 molecule was originally defined at the Fifth Workshop on Leucocyte Antigens in 1993 by two monoclonal antibodies, VMP55 and GHI/75. This cell-surface glycoprotein is expressed on B cells, monocytes, and subpopulations of T and natural killer (NK) cells, and particularly high levels are expressed by normal and neoplastic plasma cells and by hairy cell leukemia B cells. We affinity purified the CD85 antigen and obtained tryptic peptide sequence which indicated that this molecule might be ILT2, a recently described inhibitory major histocompatibility complex class I receptor of the immunoglobulin superfamily. This was confirmed by showing that both of the original anti-CD85 mAbs stained ILT2 transfectants. The cell signaling role demonstrated for ILT2 is consistent with the previously reported involvement of CD85 in T cell activation. 相似文献
11.
Sybille Lecoanet-Henchoz Christine Plater-Zyberk Pierre Graber Denise Gretener Jean-Pierre Aubry Daniel H. Conrad Jean-Yves Bonnefoy 《European journal of immunology》1997,27(9):2290-2294
CD23 is expressed on a variety of hemopoietic cells. Recently, we have reported that blocking CD23 interactions in a murine model of arthritis resulted in a marked improvement of disease severity. Here, we demonstrate that CD11b, the α chain of the β2 integrin adhesion molecule complex CD11b/CD18 expressed on monocytes interacts with CD23. Using a recombinant fusion protein (ZZ-CD23), murine CD23 was shown to bind to peritoneal macrophages and peripheral blood cells isolated from mice as well as the murine macrophage cell line, RAW. The interactions between mouse ZZ-CD23 and CD11b/CD 18-expressing cells were significantly inhibited by anti-CD11b monoclonal antibodies. A functional consequence was then demonstrated by inducing an up-regulation of interleukin-6 (IL-6) production following ZZ-CD23 incubation with monocytes. The addition of Fab fragments generated from the monoclonal antibody CD11b impaired this cytokine production by 50%. Interestingly, a positive autocrine loop was identified as IL-6 was shown to increase CD23 binding to macrophages. These results demonstrate that similar to findings using human cells, murine CD23 binds to the surface adhesion molecule, CD11b, and these interactions regulate biological activites of murine myeloid cells. 相似文献
12.
目的:研究糖化人突变(HM)CD59作为补体攻膜复合体(MAC)抑制物在糖尿病血管病病理机制中的重要作用.方法:构建2种HMCD59重组质粒, 转染CHO细胞;FCM、 Western blot筛选高表达细胞.糖化, BCECF释放试验测定糖化HM CD59和糖化HN CD59抗补体活性.ELISA测定30例糖尿病无血管病变组和30例Ⅱ型糖尿病血管病组血清PDGF-BB、 VEGF含量.结果:筛选细胞株表达率分别为59.8%、 53.7%、 54.5%;BCECF释放试验显示糖化前转染突变CD59细胞比较糖化后细胞染料释放率低(P<0.01);而正常CD59细胞比较糖化后细胞染料释放率无统计学意义. Ⅱ型糖尿病有血管病变组与糖尿病无血管病变组相比, 血清PDGF-BB、 VEGF明显增高(P<0.01).结论:证实HMCD59易糖化抗补体活性下降加速糖尿病血管病的发生发展. 相似文献
13.
Marco Alvarado Claudia Klassen Jan Cerny Vaclav Horejí Reinhold E. Schmidt 《European journal of immunology》1995,25(4):1051-1055
Previous studies on T cell activation via CD43 antigen stimulation were limited to the use of L10, a monoclonal antibody (mAb) recognizing a sialic acid-independent epitope on the CD43 molecule. Here we study the CD43 mAb MEM-59, which recognizes a neuraminidase-sensitive epitope on the CD43 molecule, for its ability to activate T lymphocytes. The antibody by itself is able to stimulate proliferation of peripheral blood mononuclear cells (PBMC) in a monocyte-dependent fashion, and to act synergistically with the mitogen phorbol 12-myristate 13-acetate. It is demonstrated that the monocyte dependence of MEM-59-induced proliferation of peripheral blood lymphocytes (PBL) cannot be attributed to cross-linking via Fc receptors on monocytes alone: F(ab′)2 fragments of MEM-59 are at least as effective as intact IgG in the induction of PBMC proliferation. The effects of MEM-59 reported here are distinct in important ways from those reported for L10. Our proliferation data are extended by the observation that MEM-59 mAb induces mobilization of intracellular Ca2+ in PBMC and in the T cell line Jurkat, while the CD3/TcR-negative Jurkat derived-mutant J.TR3-T3.5 exhibits defective signaling compared to the parent cell line. Moreover, CD3 and CD43 are shown to be present jointly in a large complex in a mild detergent lysate of the T cell line HPB-ALL. These data indicate a physical and functional association between CD3/TcR and CD43 pathways, suggesting a role for CD43 as a co-stimulatory molecule in CD3/TcR signaling, especially in T cell-antigen-presenting cell interactions. 相似文献
14.
Tajima K Demachi A Ito Y Nishida K Akatsuka Y Tsujimura K Kuwano H Mitsudomi T Takahashi T Kuzushima K 《Tissue antigens》2004,64(6):650-659
Because the epithelial cell adhesion molecule (Ep-CAM) is expressed in almost all carcinomas and human leucocyte antigen (HLA)-A*2402 is the most common allele in many ethnic groups, including Japanese, the identification of peptide sequences, which elicit HLA-A*2402-restricted Ep-CAM-specific cytotoxic T-lymphocyte (CTL) responses, would facilitate specific immunotherapy for various histological types of carcinomas. An epitope was identified through the following steps: (i) computer-based epitope prediction from the amino acid sequence of Ep-CAM, (ii) major histocompatibility complex (MHC) stabilization assay to determine the affinity of the predicted peptide with HLA-A*2402 molecules, (iii) stimulation of CD8+ T cells with peptide-pulsed dendritic cells and (iv) testing the CTL specificity by means of enzyme-linked immunospot (ELISPOT) assays, CTL assays and MHC/peptide-tetramer staining. Peripheral CD8+ T cells of four of five healthy donors after three rounds of stimulation with the peptide Ep-CAM173-181 (RYQLDPKFI) secreted interferon-gamma in ELISPOT assays when exposed to the peptide. A CTL clone specific to the peptide efficiently lysed Ep-CAM-expressing cancer cell lines in an HLA-A*2402-restricted fashion. Endogenous processing and presentation of the peptide in a lung cancer cell line were confirmed by means of cold target inhibition assays. The CTL clone was also lytic to normal bronchial epithelial cells but to a lesser extent at low effector: target ratios. All these data suggest that the peptide-specific CTL responses may play some roles both in anti-cancer and autoimmune reactions. The peptide should prove useful to study anti-Ep-CAM CTL responses among population possessing HLA-A*2402. 相似文献
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16.
J. Roth C. Zuber P. Wagner I. Blaha D. Bitter-Suermann P. U. Heitz 《The American journal of pathology》1988,133(2):227-240
The long chain form of polysialic acid characteristic of the low adhesive embryonic form of the neural cell adhesion molecule NCAM is temporally and spatially expressed in developing kidney but undetectable in normal adult kidney. Therefore, this molecule represents a developmentally regulated antigen in kidney contrasted with neural tissue, where it is also detectable in the adult brain. This investigation of 25 Wilms' tumors comprising all different histologic types demonstrates expression of this molecule under conditions of malignant growth. Immunostaining was observed in Wilms' tumors with both a monoclonal anti-polysialic acid antibody and a polyclonal anti-NCAM polypeptide antiserum. Intense cell surface staining sensitive to endosialidases specifically hydrolyzing alpha 2,8 linked (poly)sialic acid was detectable in blastemal regions, and weaker, variable labeling was seen over tubules and glomeruloid bodies. The stroma was not stained. This is evidence indicating that Wilms' tumor originates from the embryonic equivalent of induced metanephrogenic mesenchyme. It seems unlikely however, that the stroma is derived from the blastema. The same high molecular mass broad band typical of the embryonic form of NCAM was revealed by immunoblot analysis of homogenates from Wilms' tumor as well as from embryonic kidney and brain. In situ hybridization demonstrated the presence of mRNA for NCAM in all but stromal elements of Wilm's tumors. Thus, polysialic acid is present on NCAM and represents a new oncodevelopmental antigen in human kidney. Polysialic acid was greatly reduced or absent by immunohistochemistry and immunoblotting in necrotic tumor areas. 相似文献
17.
Wu ZY Gao YF Wu YH Liu W Sun M Zhai MX Qi YM Ye Y 《Scandinavian journal of immunology》2011,74(6):561-567
MAGE-4 is considered as an attractive cancer-testis (CT) antigen for tumour immunotherapy, and it is overexpressed in oesophageal carcinoma (EC). To identify MAGE-4-derived HLA-A2 restricted epitopes, native peptides and their analogues were predicted with prediction programs. The native peptide, p286 (KVLEHVVRV), and its analogues, p286-1Y2L and p286-1Y2L9L, showed potent binding affinity and stability towards HLA-A*0201 molecule. Cytotoxic T lymphocytes (CTLs) induced by p286-1Y2L9L could release IFN-γ in ELISPOT assay. In cytotoxicity assay, p286-1Y2L9L showed the capability to induce specific CTLs which could lyse the target cancer cells from both PBMCs of healthy donors and HLA-A2.1/K(b) transgenic mice. Our results indicated that the peptide p286-1Y2L9L could serve as a novel candidate epitope to develop peptide vaccines against oesophageal carcinoma. 相似文献
18.
CTL识别的HLA-A2限制性人卵巢癌相关抗原OVA66表位的鉴定 总被引:3,自引:2,他引:3
目的:鉴定CTL识别的HLA—A2限制性人卵巢癌相关抗原OVA66表位。方法:以细胞因子从外周血单个核细胞(PBMC)中诱导树突状细胞(DC),通过形态学观察和流式细胞术进行鉴定。用表位预测法选取并合成两种肽分子,分别脉冲成熟的DC,并刺激HLA—A2^ 健康人自体CD8^ T细胞,1wk后,用脉冲肽的自体PBMC以每7d的间隔刺激该CD8^ T细胞3次。以共接受4次抗原肽刺激的T细胞作为CTL,用乳酸脱氢酶(LDH)释放试验,检测CTL对靶细胞的杀伤效应。用酶联免疫斑点法(ELISPOT).检测CTL中抗原特异性分泌IFN-γ的T细胞数。结果:形态学和流式细胞术的结果显示.PBMC可诱生成熟的DC。肽1235(FLPDHINIV)诱导的CTL.可特异性杀伤1235脉冲的T2细胞和OVA66^ 、HLA—A2^ 的SW480细胞,且L235诱导的特异性分泌IFN-γ的T细胞数增加。结论:卵巢癌相关抗原OVA66的HLA—A2限制性CTL表位1235.能激发对肿瘤抗原的特异性免疫应答,为制备肿瘤特异性肽疫苗奠定了实验基础。 相似文献
19.
A. Yu. Baryshnikov T. N. Zabotina I. V. Dubinkin O. V. Korotkova A. M. Schwartsbergs L. B. Éngele V. V. Volkova K. U. Chokobaeva Z. G. Kadagidze 《Bulletin of experimental biology and medicine》1989,107(6):852-855
All-Union Oncologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR, N. N. Trapeznikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 107, No. 6, pp. 729–731, June, 1989. 相似文献
20.
Molecular cloning of an Echinococcus granulosus protein expressing an immunogenic epitope of antigen 5. 总被引:5,自引:0,他引:5
cDNA was synthesized from RNA extracted from Echinococcus granulosus protoscoleces and cloned in the lambda gt11 expression vector. A pool of 5 E. granulosus patient sera was used to screen the library and allowed the selection of 13 clones. Ten of these were shown to be identical, among which clone 6 (Eg6) was chosen for further analysis. The nucleotide sequence (456-bp) presented an entire open reading frame coding for 152 amino acids. The fusion protein (FP6) was recognized by a mouse monoclonal antibody (EG 02 154/12) specific for E. granulosus antigen 5. Moreover, the presence of antibodies to FP6 seemed to be correlated to the ability of sera from hydatidosis patients to immunoprecipitate antigen 5. These results indicate that the cloned protein could be used as a standardized antigen for the diagnosis of hydatidosis. 相似文献