Binding of nucleosomes to a cell surface receptor: redistribution and endocytosis in the presence of lupus antibodies.


:In the present study, we sought evidence for a surface nucleosome receptor in the fibroblastic cell line CV-1, and questioned whether anti-double-stranded (ds) DNA and/or anti-histone autoantibodies could recognize and influence the fate of cell surface-bound nucleosomes. 125I-labeled mononucleosomes were shown to bind to the cell layer in a specific, concentration-dependent and a saturable manner. Scatchard analysis revealed the presence of two binding sites: a high-affinity site with a Kd of approximately 7nM and a low-affinity site (Kd approximately 400 nM) with a high capacity of 9 x 10(7) sites. Visualization of bound mononucleosomes by fluorescence revealed staining on both the cell surface and the extracellular matrix (ECM). Purified mononucleosome-derived ds DNA (180-200 bp) was found to complete for binding of 125I-mononucleosomes on the low-affinity site, to stain exclusively the ECM in immunofluorescence, and to precipitate three specific proteins of 43, 180 and 240 kDa from 125-I-labeled cell lysates. Nucleosomes were found to precipitate not only the 180-kDa ds DNA-reactive component, but also a unique protein of 50 kDa, suggesting that this protein is a cell surface receptor for nucleosomes on these fibroblasts. Once bound on the cell surface, mononucleosomes were recognized and secondarily complexed by lupus anti-ds DNA or anti-histone antibodies (i.e. anti-nucleosome antibodies), thus forming immune complexes in situ. The presence of these complexing auto-antibodies was found dramatically to enhance the kinetics of mononucleosome internalization. Following the internalization of the nucleosome-anti-nucleosome complexes by immunofluorescence, we observed the formation of vesicles at the edge of the cells by 5-10 min which moved toward the perinuclear region by 20-30 min. By means of double-fluorescence labeling and proteolytic treatment, these fluorescent vesicles were shown to be in the cytoplasm, suggesting true endocytosis of nucleosome-anti-nucleosome immune complexes. As shown by confocal microscopy, at no stage of this endocytic process was there any indication that coated pits or coated vesicles participated. Co-distribution of the endocytic vesicles with regions rich in actin filaments and inhibition of endocytosis of nucleosome-anti-nucleosome complexes by disruption of the microfilament network with cytochalasin D suggest a mechanism mediated by the cytoskeleton. Taken together, our data provide evidence for the presence of a surface nucleosome receptor. We also show that anti-ds DNA and anti-histone antibodies can form nucleosome-anti-nucleosome immune complexes in situ at the cell surface, and thus dramatically enhance the kinetics of nucleosome endocytosis.


Eur J Immunol


Koutouzov S,Cabrespines A,Amoura Z,Chabre H,Lotton C,Bach JF




Has Abstract


1996-02-01 00:00:00












  • The TNF receptor family member CD27 signals to Jun N-terminal kinase via Traf-2.

    abstract::CD27 is a lymphocyte-specific member of the TNF receptor (TNFR) family. It is a costimulatory molecule for peripheral T cells, as defined by its ability to enhance the TCR-induced proliferative response. We show here that CD27 augments TCR-induced Jun N-terminal kinase (JNK) activity in primary murine lymph node T cel...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Gravestein LA,Amsen D,Boes M,Calvo CR,Kruisbeek AM,Borst J

    更新日期:1998-07-01 00:00:00

  • Effects of human immunodeficiency virus type 1 on CD4 lymphocyte subset activation.

    abstract::The pathogenesis of the decline of CD4 lymphocyte counts accompanying the typical course of HIV-1 infection is not completely defined and might be related to a differential susceptibility of naive and memory cells to HIV-1 exposure. Here, we examined the effects induced by heat-inactivated HIV-1 virions on these lymph...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Masci AM,Paz FL,Borriello A,Cassano S,Della Pietra V,Stoiber H,Matarese G,Della Ragione F,Zappacosta S,Racioppi L

    更新日期:1999-06-01 00:00:00

  • Age-related increase of CD45RO+ lymphocytes in physically active adults.

    abstract::The CD45RO phenotype of peripheral blood CD4+ and CD8+ lymphocytes were determined in physically active males (n = 171) and females (n = 70) ranging in age from 15-68 years. Direct immunofluorescence and dual color flow cytometry was performed for analysis. Absolute cell numbers (r = 0.473) and percentages of CD4+ CD4...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Gabriel H,Schmitt B,Kindermann W

    更新日期:1993-10-01 00:00:00

  • Aggravation of experimental cutaneous leishmaniasis in mice by administration of interleukin 3.

    abstract::Previous studies from our laboratory have shown that some in vitro maintained Leishmania major-specific L3T4+ T cells were capable of exacerbating cutaneous leishmaniasis after adoptive transfer to normal syngeneic mice. Results presented in this report show that these cells released substantial amounts of interleukin...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Feng ZY,Louis J,Kindler V,Pedrazzini T,Eliason JF,Behin R,Vassalli P

    更新日期:1988-08-01 00:00:00

  • The biology of myeloid-derived suppressor cells: the blessing and the curse of morphological and functional heterogeneity.

    abstract::Myeloid-derived suppressor cells (MDSC) play an important role in the cellular network regulating immune responses in cancer, chronic infectious diseases, autoimmunity, and in other pathological conditions. Morphological, phenotypic and functional heterogeneity is a hallmark of MDSC. This heterogeneity demonstrates th...

    journal_title:European journal of immunology

    pub_type: 杂志文章,评审


    authors: Youn JI,Gabrilovich DI

    更新日期:2010-11-01 00:00:00

  • Antibody-independent activation of complement by human peripheral B lymphocytes.

    abstract::Normal human peripheral blood lymphocytes were shown to activate complement in normal human serum (NHS). This activation led to C3 fixation on the cell membrane, which in turn was visualized by fluorescence. The reaction occurred in the absence of detectable amounts of antibodies, since an agammaglobulinemic patient's...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Gutiérrez C,Vega J,Kreisler M

    更新日期:1979-01-01 00:00:00

  • Human immunodeficiency virus gp120 and derived peptides activate protein tyrosine kinase p56lck in human CD4 T lymphocytes.

    abstract::Human immunodeficiency virus binds to CD4 T lymphocytes by interaction between its envelope glycoprotein gp120 and the CD4 molecule. The latter is non-covalently associated with a src-related tyrosine kinase, p56lck. CD4 cross-linking increases the activity of p56lck, leading to phosphorylation of several cellular sub...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Hivroz C,Mazerolles F,Soula M,Fagard R,Graton S,Meloche S,Sekaly RP,Fischer A

    更新日期:1993-03-01 00:00:00

  • Leptin: nourishment for the immune system.

    abstract::Leptin, a protein produced by adipocytes, exerts several functions, including modulation of the immune response. A report in this issue of the European Journal of Immunology describes for the first time the effect of either leptin receptor deficiency or blockade on murine dendritic cell (DC) maturation, survival and f...

    journal_title:European journal of immunology

    pub_type: 杂志文章,评审


    authors: Fantuzzi G

    更新日期:2006-12-01 00:00:00

  • IL-33 is a chemoattractant for human Th2 cells.

    abstract::IL-33 is a novel cytokine of the IL-1 family and mediates its biological effect via the receptor ST2, which is selectively expressed on Th2 cells but not Th1 cells. IL-33 drives production of Th2-associated cytokines including IL-5 and IL-13 and thereby promotes defense and pathology in mucosal organs. Cell locomotion...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Komai-Koma M,Xu D,Li Y,McKenzie AN,McInnes IB,Liew FY

    更新日期:2007-10-01 00:00:00

  • Double-negative thymocyte subsets in CD3 zeta chain-deficient mice: absence of HSA+CD44-CD25- cells.

    abstract::Double-negative (DN) thymocyte subsets were examined in mice deficient in the CD3 zeta chain (zeta-/-). The HSA+CD44-CD25- subset was found to be missing, and DN thymocytes seemed to differentiate directly from HSA+CD25+CD44- cells to double-positive (DP) cells. When fetal thymic ontogeny was examined, we found a mark...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Crompton T,Moore M,MacDonald HR,Malissen B

    更新日期:1994-08-01 00:00:00

  • IL-33 broadens its repertoire to affect DC.

    abstract::IL-33 is a novel multi-functional IL-1 family member that, in contrast to other family members, is associated with Th2 responses. IL-33 signals via a heterodimer composed of its receptor, IL-1 receptor-like-1 (IL-1RL1), more commonly known as ST2L, and the IL-1R accessory protein. ST2L is expressed by endothelial cell...

    journal_title:European journal of immunology

    pub_type: 评论,杂志文章


    authors: Turnquist HR,Thomson AW

    更新日期:2009-12-01 00:00:00

  • TCR signalling network organization at the immunological synapses of murine regulatory T cells.

    abstract::Regulatory T (Treg) cells require T-cell receptor (TCR) signalling to exert their immunosuppressive activity, but the precise organization of the TCR signalling network compared to conventional T (Tconv) cells remains elusive. By using accurate mass spectrometry and multi-epitope ligand cartography (MELC) we character...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: van Ham M,Teich R,Philipsen L,Niemz J,Amsberg N,Wissing J,Nimtz M,Gröbe L,Kliche S,Thiel N,Klawonn F,Hubo M,Jonuleit H,Reichardt P,Müller AJ,Huehn J,Jänsch L

    更新日期:2017-12-01 00:00:00

  • Genes encoded in the major histocompatibility complex affecting the generation of peptides for TAP transport.

    abstract::The B cell line 721.174 has lost the ability to present intracellular antigens to major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL). This phenotype results from a homozygous deletion in the MHC that includes the peptide transporter genes TAP1 and TAP2, and the proteasome subunits ...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Cerundolo V,Kelly A,Elliott T,Trowsdale J,Townsend A

    更新日期:1995-02-01 00:00:00

  • Phenotypic and functional analysis of B lymphopoiesis in interleukin-7-transgenic mice: expansion of pro/pre-B cell number and persistence of B lymphocyte development in lymph nodes and spleen.

    abstract::Transgenic mice in which mouse interleukin (IL)-7 cDNA is expressed under the control of the mouse major histocompatibility complex (MHC) class II (E alpha) promoter develop a lymphoproliferative disease characterized by the early polyclonal expansion of T cells followed in many cases by the development of lymphomas o...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Mertsching E,Grawunder U,Meyer V,Rolink T,Ceredig R

    更新日期:1996-01-01 00:00:00

  • Differential contribution of Lck and Fyn protein tyrosine kinases to intraepithelial lymphocyte development.

    abstract::The developmental stages and the role of protein tyrosine kinases (PTK) in the maturation of CD3+CD8 alpha alpha+ intraepithelial lymphocytes (IEL) have not been extensively characterized. However, comparisons of thymic and extrathymic T cell development indicate that these processes involve some distinct signaling an...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Page ST,van Oers NS,Perlmutter RM,Weiss A,Pullen AM

    更新日期:1997-02-01 00:00:00

  • Recombinant cytomegalovirus glycoprotein gB (UL55) induces an autoantibody response to the U1-70 kDa small nuclear ribonucleoprotein.

    abstract::Human cytomegalovirus (CMV) infection can be life threatening in the immune compromised and is associated with congenital defects and / or mental retardation in the neonate. The demonstrated association between CMV infection and rheumatoid factor (RF) raised the possibility of an induction of an autoimmune response up...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Curtis HA,Singh T,Newkirk MM

    更新日期:1999-11-01 00:00:00

  • Natural variations at position 93 of the invariant Vα24-Jα18 α chain of human iNKT-cell TCRs strongly impact on CD1d binding.

    abstract::Human invariant natural killer T (NKT) cell TCRs bind to CD1d via an "invariant" Vα24-Jα18 chain (iNKTα) paired to semi-invariant Vβ11 chains (iNKTβ). Single-amino acid variations at position 93 (p93) of iNKTα, immediately upstream of the "invariant" CDR3α region, have been reported in a substantial proportion of huma...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Sanderson JP,Waldburger-Hauri K,Garzón D,Matulis G,Mansour S,Pumphrey NJ,Lissin N,Villiger PM,Jakobsen B,Faraldo-Gómez JD,Gadola SD

    更新日期:2012-01-01 00:00:00

  • Specific microbiota enhances intestinal IgA levels by inducing TGF-β in T follicular helper cells of Peyer's patches in mice.

    abstract::In humans and mice, mucosal immune responses are dominated by IgA antibodies and the cytokine TGF-β, suppressing unwanted immune reactions but also targeting Ig class switching to IgA. It had been suggested that eosinophils promote the generation and maintenance of mucosal IgA-expressing plasma cells. Here, we demonst...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Beller A,Kruglov A,Durek P,von Goetze V,Werner K,Heinz GA,Ninnemann J,Lehmann K,Maier R,Hoffmann U,Riedel R,Heiking K,Zimmermann J,Siegmund B,Mashreghi MF,Radbruch A,Chang HD

    更新日期:2020-06-01 00:00:00

  • Human basophils release interleukin-4 after stimulation with Schistosoma mansoni egg antigen.

    abstract::The elevated interleukin (IL)-4 and IgE production in Schistosoma mansoni infection seems to be induced essentially by the egg stage of the parasite. The underlying mechanism, however, is not known. Since basophils from human peripheral blood can produce IL-4, we asked, whether soluble S. mansoni egg antigens (SEA) wo...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Falcone FH,Dahinden CA,Gibbs BF,Noll T,Amon U,Hebestreit H,Abrahamsen O,Klaucke J,Schlaak M,Haas H

    更新日期:1996-05-01 00:00:00

  • CpG motifs of bacterial DNA exacerbate colitis of dextran sulfate sodium-treated mice.

    abstract::Inflammatory bowel disease (IBD) is characterized by a dysregulated intestinal immune response with elevated levels of the Th1 cytokines TNF, IL-12 and IFN-gamma. The luminal flora has been implicated as a major factor contributing to the initiation and perpetuation of chronic intestinal inflammation by as yet unknown...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Obermeier F,Dunger N,Deml L,Herfarth H,Schölmerich J,Falk W

    更新日期:2002-07-01 00:00:00

  • FTY720 enhances the activation-induced apoptosis of donor T cells and modulates graft-versus-host disease.

    abstract::FTY720 is a novel immunosuppressant that improves the outcomes after solid organ and bone marrow transplantation (BMT) due to the sequestration of T cells into LN. We tested the hypothesis that the sequestration of donor T cells in LN by FTY720 would enhance their interaction with host APC, thus causing a greater degr...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Hashimoto D,Asakura S,Matsuoka K,Sakoda Y,Koyama M,Aoyama K,Tanimoto M,Teshima T

    更新日期:2007-01-01 00:00:00

  • AMPK: a metabolic switch for CD8+ T-cell memory.

    abstract::Adenosine monophosphate-activated protein kinase (AMPK) is a serine/threonine kinase and is crucial for cellular energy homeostasis. The exact role of AMPK during memory CD8(+) T-cell differentiation, a process that changes from the metabolically active state of effector T cells to one of quiescence in memory cells is...

    journal_title:European journal of immunology

    pub_type: 评论,杂志文章


    authors: Araki K,Ahmed R

    更新日期:2013-04-01 00:00:00

  • An HLA-B35-restricted epitope modified at an anchor residue results in an antagonist peptide.

    abstract::Peptides associated with HLA-B35 commonly have a proline or occasionally a serine residue in the P2 anchor position of the peptide, with a tyrosine at the C terminus. Based on this motif, we identified an octamer epitope from influenza A matrix protein which is presented by HLA-B35. The requirements for MHC binding an...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Dong T,Boyd D,Rosenberg W,Alp N,Takiguchi M,McMichael A,Rowland-Jones S

    更新日期:1996-02-01 00:00:00

  • Recognition by major histocompatibility complex class I-restricted cytolytic T lymphocytes of cells expressing vaccinia-encoded viral and class I proteins.

    abstract::Target cells expressing influenza virus hemagglutinin (HA) could be recognized by cytotoxic T lymphocytes (CTL) in conjunction with the murine major histocompatibility complex class I antigen, H-2Kd, when both antigens were encoded by recombinant vaccinia virus. This recognition occurred if HA and H-2Kd were encoded b...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Andrew ME,Coupar BE,Boyle DB,Blanden RV

    更新日期:1987-10-01 00:00:00

  • Identification of a novel subpopulation of germinal center B cells characterized by expression of IgD and CD70.

    abstract::CD27, which belongs to the tumor necrosis factor receptor family, is expressed on germinal center (GC) but not on naive B cells, suggesting an important function of this molecule in the regulation of the GC reaction. We described here the expression of CD70, which is the ligand for CD27. We observed that in most tonsi...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Lens SM,Keehnen RM,van Oers MH,van Lier RA,Pals ST,Koopman G

    更新日期:1996-05-01 00:00:00

  • Genetic control of B cell function. III. IgVH-controlled polymorphism in the frequencies of B cells that recognize xenogeneic red blood cells.

    abstract::Previous work has shown that the primary IgM plaque-forming cell response of inbred mice to xenogeneic red blood cells (RBC) including sheep, horse and chicken RBC is under the control of two polymorphic genes or sets of genes, one linked to the Igh linkage group and the other of unknown linkage but unlinked to H-2 an...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Saizawa KM,Melchers I,Eichmann K

    更新日期:1985-02-01 00:00:00

  • Mast cells in allergy and infection: versatile effector and regulatory cells in innate and adaptive immunity.

    abstract::Mast cells are widely distributed in tissues, particularly near surfaces exposed to the environment. Mast cells can be activated to secrete diverse mediators and cytokines by IgE and specific Ag and many other stimuli, including products derived from either pathogens or the host during innate immune responses. Althoug...

    journal_title:European journal of immunology

    pub_type: 杂志文章,评审


    authors: Galli SJ,Tsai M

    更新日期:2010-07-01 00:00:00

  • Transgenic expression of an immunologically privileged retinal antigen extraocularly enhances self tolerance and abrogates susceptibility to autoimmune uveitis.

    abstract::Interphotoreceptor retinoid-binding protein (IRBP) is an immunologically privileged retinal antigen that can elicit experimental autoimmune uveitis (EAU). The nature and extent of tolerance to immunologically privileged self antigens is poorly understood. To investigate whether transgenic expression of IRBP extraocula...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Xu H,Wawrousek EF,Redmond TM,Nickerson JM,Wiggert B,Chan CC,Caspi RR

    更新日期:2000-01-01 00:00:00

  • Immunity to transplantable carcinogen-induced fibrosarcomas in B2/B2 chickens. III. Tumor growth inhibition by local delayed hypersensitivity reactions to unrelated antigens.

    abstract::Delayed hypersensitivity (DH) reaction to human Ig, corynebacterium parvum or allogeneic cells at the site of tumor cell injection, suppressed the fibrosarcoma (SCFS) growth in chickens. Spleen cells of SC chickens sensitized to human Ig or C. parvum suppressed SCFS growth when adoptively transferred with tumor cells,...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Palladino MA,Thorbecke GJ

    更新日期:1978-04-01 00:00:00

  • Mutations of the gene FNIP1 associated with a syndromic autosomal recessive immunodeficiency with cardiomyopathy and pre-excitation syndrome.

    abstract::AMPK (adenosine monophosphate-activated protein kinase) is phosphorylated (AMPK-P) in response to low energy through allosteric activation by Adenosine mono- or diphosphate (AMP/ADP). Folliculin (FLCN) and the FLCN-interacting proteins 1 and 2 (FNIP1, 2) modulate AMPK. FNIP1 deficiency patients have a AMPK-P gain of f...

    journal_title:European journal of immunology

    pub_type: 信件


    authors: Niehues T,Özgür TT,Bickes M,Waldmann R,Schöning J,Bräsen J,Hagel C,Ballmaier M,Klusmann JH,Niedermayer A,Pannicke U,Enders A,Dückers G,Siepermann K,Hempel J,Schwarz K,Viemann D

    更新日期:2020-07-01 00:00:00