Immunodominant T-cell epitopes of hnRNP-A2 associated with disease activity in patients with rheumatoid arthritis.

Abstract:

:The heterogeneous nuclear ribonucleoprotein A2 (hnRNP-A2) has been described as an important autoantigen in rheumatoid arthritis (RA) since it is targeted by autoantibodies, autoreactive T cells, and is aberrantly expressed in synovial cells in patients. To identify hnRNP-A2-specific T-cell epitopes possibly associated with pathogenicity, we used an innovative approach. We first scanned 280 overlapping hnRNP-A2 peptides for binding to the RA-associated class II molecules HLA-DR4 and HLA-DR1, leading to a comprehensive selection of binders. The selected peptides were tested in IFN-gamma-specific ELISPOT assay: PBMC from 18% of RA patients showed a significant IFN-gamma response to hnRNP-A2 peptides, 15% to the overlapping sequences 117-133 and/or 120-133, whereas PBMC from healthy individuals tested negative. We measured proliferative responses to these two peptides in another cohort of patients with RA or osteoarthritis: positive responses were found in 28% of RA, but also in 11% of osteoarthritis patients and these responses could be blocked by anti-MHC class II Ab. Remarkably, the presence of 117/120-133-specific T cells was significantly associated with active disease in RA patients, and bone erosion appeared to be more common in T-cell positive patients. These data suggest involvement of hnRNP-A2 specific cellular autoimmune responses in RA pathogenesis.

journal_name

Eur J Immunol

authors

Trembleau S,Hoffmann M,Meyer B,Nell V,Radner H,Zauner W,Hammer J,Aichinger G,Fischer G,Smolen J,Steiner G

doi

10.1002/eji.200939482

subject

Has Abstract

pub_date

2010-06-01 00:00:00

pages

1795-808

issue

6

eissn

0014-2980

issn

1521-4141

journal_volume

40

pub_type

杂志文章
  • Catalase inhibits nitric oxide synthesis and the killing of intracellular Leishmania major in murine macrophages.

    abstract::Mouse peritoneal macrophages activated with interferon-gamma (IFN-gamma) and lipopolysaccharide produce substantial amounts of nitric oxide (NO), which correlates with the elimination of the intracellular protozoan parasite Leishmania major. Both the production of NO and the leishmanicidal function of the activated ma...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830220223

    authors: Li Y,Severn A,Rogers MV,Palmer RM,Moncada S,Liew FY

    更新日期:1992-02-01 00:00:00

  • Triggering of the alternative pathway of human T cell activation involves members of the T 200 family of glycoproteins.

    abstract::The present report describes functional characteristics of a monoclonal antibody (mAb), TA/211, which is reactive with a common determinant of the human CD45 molecules. When added to purified testing human T cells, TA/211, which is itself not mitogenic, leads to a strong proliferative response in combination with subm...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830190226

    authors: Schraven B,Roux M,Hutmacher B,Meuer SC

    更新日期:1989-02-01 00:00:00

  • Synergistic OX40 and CD30 signals sustain CD8+ T cells during antigenic challenge.

    abstract::Prior to acquiring a memory phenotype, antigen-activated CD8(+) T cells need to expand and then undergo a contraction phase. Utilizing two different antigenic stimuli, we provide evidence that the tumor necrosis factor receptors OX40 and CD30 integrate synergistic signals during the expansion phase to help maintain CD...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200939424

    authors: Bekiaris V,Gaspal F,Kim MY,Withers DR,Sweet C,Anderson G,Lane PJ

    更新日期:2009-08-01 00:00:00

  • Mini-review: Specificity and expression of CIITA, the master regulator of MHC class II genes.

    abstract::The class II transactivator (CIITA) has been referred to as the "master control factor" for the expression of MHC class II (MHCII) genes. As our knowledge on the specificity and function of CIITA grows, it is becoming increasingly evident that this sobriquet is entirely justified. First, despite extensive investigatio...

    journal_title:European journal of immunology

    pub_type: 杂志文章,评审

    doi:10.1002/eji.200424964

    authors: LeibundGut-Landmann S,Waldburger JM,Krawczyk M,Otten LA,Suter T,Fontana A,Acha-Orbea H,Reith W

    更新日期:2004-06-01 00:00:00

  • Presence of T 145 on cytolytic T cell lines and their lectin-resistant mutants.

    abstract::Murine cytolytic T cell lines have been analyzed for the expression of two surface glycoproteins called T145 and T130. T145, known to be expressed by activated cytolytic T cells, is also expressed by such lines, but T130, which has been described by a universal T cell marker, is not. Our results suggest a structural r...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830101111

    authors: Conzelmann A,Pink R,Acuto O,Mach JP,Dolivo S,Nabholz M

    更新日期:1980-11-01 00:00:00

  • Homotypic aggregation of human cell lines by HLA class II-, class Ia- and HLA-G-specific monoclonal antibodies.

    abstract::Major histocompatibility complex (MHC) class II molecules have been implicated in cell adhesion in two ways. In addition to the well-established role of class II antigens in low-affinity adhesion provided by interactions between class II and CD4, recent data indicated that class II may also induce adhesion between T a...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830210921

    authors: Odum N,Ledbetter JA,Martin P,Geraghty D,Tsu T,Hansen JA,Gladstone P

    更新日期:1991-09-01 00:00:00

  • Purified lymphocyte function-associated antigen-3 and T11 target structure are active in CD2-mediated T cell stimulation.

    abstract::In this study we have used cells expressing LFA-3 or T11TS, the human and sheep forms of the ligand of CD2, as well as the purified LFA-3 and T11TS molecules themselves to study their effects on T cell activation via the CD2-mediated "alternative pathway". Sheep red blood cells, which bind to CD2 via T11TS in E-rosett...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830171227

    authors: Tiefenthaler G,Hünig T,Dustin ML,Springer TA,Meuer SC

    更新日期:1987-12-01 00:00:00

  • Interleukin-6 functions in autoimmune encephalomyelitis: a study in gene-targeted mice.

    abstract::The encephalitogenic peptide pMOG 35-55 from the myelin oligodendrocyte glycoprotein was used to induce experimental autoimmune encephalomyelitis (EAE) in H-2b mice with the interleukin-6 (IL-6) gene intact or disrupted. The IL-6+/+ mice developed a chronic form of EAE ascending paralysis, whereas the IL-6-/- mice wer...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199805)28:05<1727::AID-IMM

    authors: Mendel I,Katz A,Kozak N,Ben-Nun A,Revel M

    更新日期:1998-05-01 00:00:00

  • Suppressive effect of interferon-gamma on the BCL1 cell-dependent interleukin 5 bioassay.

    abstract::Proliferation of BCL1 cells, generally used for the measurement of murine interleukin (IL)5, is shown to be strongly suppressed by interferon (IFN)-gamma. This effect can be abrogated by the addition of anti-IFN-gamma antibodies. Thus, the IL5 activity of culture supernatants derived from T cells simultaneously produc...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830190726

    authors: Lohoff M,Sommer F,Röllinghoff M

    更新日期:1989-07-01 00:00:00

  • IL-12 directs severe renal injury, crescent formation and Th1 responses in murine glomerulonephritis.

    abstract::Glomerular crescent formation characterizes severe glomerulonephritis (GN). Evidence suggests that crescent formation results from a delayed-type hypersensitivity-like Th1 response. As IL-12 directs Th1 responses, we tested the hypothesis that IL-12 is important in crescentic GN. Neutralization of IL-12 attenuated cre...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199901)29:01<1::AID-IMMU1>

    authors: Kitching AR,Tipping PG,Holdsworth SR

    更新日期:1999-01-01 00:00:00

  • Mitochondrial and cytosolic roles of PINK1 shape induced regulatory T-cell development and function.

    abstract::Mutations in PTEN-induced kinase 1 (PINK1), a serine/threonine kinase linked to familial early-onset Parkinsonism, compromise mitochondrial integrity and metabolism and impair AKT signaling. As the activation of a naïve T cell requires an AKT-dependent reorganization of a cell's metabolic machinery, we sought to deter...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201343571

    authors: Ellis GI,Zhi L,Akundi R,Büeler H,Marti F

    更新日期:2013-12-01 00:00:00

  • Multiple cross-reactive self-ligands for Borrelia burgdorferi-specific HLA-DR4-restricted T cells.

    abstract::T cell recognition of self antigens is a key event in the pathogenesis of autoimmune diseases. To date, the initial events that trigger autoreactive T cells are unknown. The "molecular mimicry" hypothesis predicts that during an infection T cells that recognize both a microbial antigen and a related self peptide becom...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/1521-4141(200002)30:2<448::AID-IMMU448>3.0

    authors: Maier B,Molinger M,Cope AP,Fugger L,Schneider-Mergener J,Sønderstrup G,Kamradt T,Kramer A

    更新日期:2000-02-01 00:00:00

  • Different repertoires of mouse T cells for bovine insulin presented by syngeneic and allogeneic cells.

    abstract::Splenic T cells were primed, after removal of alloreactive cells, to beef insulin on allogeneic antigen-presenting cells (APC). The fine specificity of in vitro secondary response was tested in combinations H-2b (responder) T cell-H-2k (nonresponder) APC, and vice versa, using separated chains of beef and pork insulin...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830130810

    authors: Ishii N,Klein J,Nagy ZA

    更新日期:1983-08-01 00:00:00

  • Primary responses of human T cells to mycobacteria: a frequent set of gamma/delta T cells are stimulated by protease-resistant ligands.

    abstract::T lymphocyte subsets expressing either T cell receptor alpha/beta or gamma/delta were selected from human peripheral blood T cells and proliferative responses to molecular mass-fractionated mycobacterial lysates were determined. alpha/beta T cells primarily responded to fractions greater than 30 kDa whereas gamma/delt...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830200534

    authors: Pfeffer K,Schoel B,Gulle H,Kaufmann SH,Wagner H

    更新日期:1990-05-01 00:00:00

  • On the significance of CD8 alpha alpha expression for T cell memory.

    abstract::Longitudinal studies on the kinetics of viral antigen specific CD8 T cell responses have led to a model whereby a relatively small subset of the primary effector CD8 T cells expanding after the first week of acute viral infection initiate a program of cell survival and differentiation into long lived memory T cells. T...

    journal_title:European journal of immunology

    pub_type: 评论,杂志文章

    doi:10.1002/eji.200535516

    authors: Romero P,Cerottini JC,Luescher I

    更新日期:2005-11-01 00:00:00

  • Membrane anchoring and spontaneous release of CD16 (FcR III) by natural killer cells and granulocytes.

    abstract::CD16 is an IgG Fc receptor that is predominantly expressed on human natural killer (NK) cells and granulocytes. The CD16 antigen expressed on neutrophils is a 50 to 70-kDa glycoprotein attached to the plasma membrane by a phosphatidylinositol-glycan linkage that is susceptible to cleavage by phosphatidylinositol-speci...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830190431

    authors: Lanier LL,Phillips JH,Testi R

    更新日期:1989-04-01 00:00:00

  • Immunochemical and biochemical study of a human Fcmu-like fragment (mu-chain disease).

    abstract::An abnormal protein, from a petient with mu-chain disease has been studied: protein BUR. It is devoid of the F (ab'')2 mu fragment; molecular weight determinations and immunological data identify the protein as a F(c) 5 mu fragment. Similarly, carbohydrate determinations and proteolysis experiments relate it to a Fcmu...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830050306

    authors: Lebreton JP,Ropartz C,Rousseaus J,Roussel P,Dautrevaus M,Biserte G

    更新日期:1975-03-01 00:00:00

  • Membrane lymphotoxin contributes to anti-leishmanial immunity by controlling structural integrity of lymphoid organs.

    abstract::Lymphotoxin (LT)alpha in combination with LTbeta forms membrane-bound heterotrimeric complexes with a crucial function in lymph node (LN) organogenesis and correct morphogenesis of secondary lymphoid tissue. To study the role of membrane LT (mLT) in lymphoid tissue organogenesis we generated an LTbeta-deficient mouse ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/1521-4141(200207)32:7<1993::AID-IMMU1993>3

    authors: Wilhelm P,Riminton DS,Ritter U,Lemckert FA,Scheidig C,Hoek R,Sedgwick JD,Körner H

    更新日期:2002-07-01 00:00:00

  • Immunoglobulin heavy chain germ-line JH-C mu transcription in human precursor B lymphocytes initiates in a unique region upstream of DQ52.

    abstract::From human precursor B cells which had both immunoglobulin (Ig) heavy (H) chain loci in germ-line configuration, various IgH chain germ-line transcripts were isolated and sequenced. These transcripts were shown to contain sequences derived from the JH region, the IgH chain enhancer element or the Ig switch region. A n...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830250142

    authors: Thompson A,Timmers E,Schuurman RK,Hendriks RW

    更新日期:1995-01-01 00:00:00

  • Tumor-specific T helper activity can be abrogated by two distinct suppressor cell mechanisms.

    abstract::Tumor-specific helper T cell activity was detected in the spleens of tumor-bearing mice using a sensitive, simple and reproducible in vitro assay based on those previously described for soluble hapten-carrier antigens. Helper activity disappears when the tumor is large. This is coincident with the appearance of two di...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830120809

    authors: Howie S,McBride WH

    更新日期:1982-08-01 00:00:00

  • Modulation of E2F activity in primary mouse B cells following stimulation via surface IgM and CD40 receptors.

    abstract::Since signals via CD40 and the B cell receptor are known to synergize to induce B cell activation, we have analyzed the pocket protein/E2F complexes in mouse B lymphocytes following stimulation by anti-IgM, anti-CD40, alone or together. We find that E2F4 and DP1 form the predominant E2F heterodimers in the G0 and G1 p...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199910)29:10<3380::AID-IMM

    authors: Lam EW,Glassford J,van der Sman J,Banerji L,Pizzey AR,Shaun N,Thomas B,Klaus GG

    更新日期:1999-10-01 00:00:00

  • Th1 and Th2 CD4+ T cell clones specific for Plasmodium chabaudi but not for an unrelated antigen protect against blood stage P. chabaudi infection.

    abstract::The host protective immune response to blood stage malaria infection was studied using Plasmodium chabaudi chabaudi (P.chabaudi) in NIH mice. It has been shown previously that CD4+ cells are critically required for protection against erythrocytic infection. Mice lacking a functional CD4+ cell compartment suffer unremi...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830240124

    authors: Taylor-Robinson AW,Phillips RS

    更新日期:1994-01-01 00:00:00

  • Recirculating and germinal center B cells differentiate into cells responsive to polysaccharide antigens.

    abstract::Antibodies against bacterial capsular polysaccharides play a critical protective role. Responses to these antigens can occur without the help or control of T cells and are associated with marginal zone (MZ) B cells. Capsular antigens are diverse and some cross-react with self-carbohydrate epitopes. This diversity may ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/immu.200310003

    authors: Vinuesa CG,Sze DM,Cook MC,Toellner KM,Klaus GG,Ball J,MacLennan IC

    更新日期:2003-02-01 00:00:00

  • Chronic myelogenous leukemia-derived basophilic granulocytes express a functional active receptor for the anaphylatoxin C3a.

    abstract::The receptor for the inflammatory peptide C3a has scarcely been examined on human cells. This work demonstrates that human tumor-derived basophilic granulocytes express C3a receptors, and presents parts of the hitherto unknown C3a-signal transduction. When incubated with IL-3, these cells specifically liberated histam...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830230239

    authors: Kretzschmar T,Jeromin A,Gietz C,Bautsch W,Klos A,Köhl J,Rechkemmer G,Bitter-Suermann D

    更新日期:1993-02-01 00:00:00

  • Xenogeneic recognition of soluble and cell surface HLA class II antigens by proliferative murine T cells.

    abstract::In order to characterize the murine anti-human xenogeneic mixed lymphocyte reactions (MLR), we studied T cell proliferative responses against various human lymphoid cells by immunization of mice either with cellular or purified HLA-DR antigens. Data presented here indicated that small amounts of soluble HLA-DR antigen...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830171103

    authors: Viguier M,Lotteau V,Charron D,Debré P

    更新日期:1987-11-01 00:00:00

  • Treatment and management of primary antibody deficiency: German interdisciplinary evidence-based consensus guideline.

    abstract::This evidence-based clinical guideline provides consensus-recommendations for the treatment and care of patients with primary antibody deficiencies (PADs). The guideline group comprised 20 clinical and scientific expert associations of the German, Swiss, and Austrian healthcare system and representatives of patients. ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.202048713

    authors: Hanitsch L,Baumann U,Boztug K,Burkhard-Meier U,Fasshauer M,Habermehl P,Hauck F,Klock G,Liese J,Meyer O,Müller R,Pachlopnik-Schmid J,Pfeiffer-Kascha D,Warnatz K,Wehr C,Wittke K,Niehues T,von Bernuth H

    更新日期:2020-10-01 00:00:00

  • Stimulation and suppression of rat mast cell functions by alloantibodies.

    abstract::The stimulatory as well as the inhibitory capacity of alloantisera has been investigated with respect to rat mast cell functions. Alloantibody against alloantigens coded for by the major histocompatibility (H-1) gene region promoted histamine release from purified LEW mast cells. This process was found to be complemen...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830060813

    authors: Mossmann H,Lauer W,Vortisch U,Gunther E,Bazin H,Hammer DK

    更新日期:1976-08-01 00:00:00

  • Defined antigens secreted by the larvae of schistosomes protect against schistosomiasis: induction of cytotoxic antibodies in the rat and the monkey.

    abstract::The study of the immunology of schistosomiasis has allowed a clear understanding of the basic mechanisms of resistance, emphasizing the important role played by cellular and humoral factors. Whereas the production of polyclonal or monoclonal antibodies and the precise inventory of immune effector mechanisms in the rat...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830151205

    authors: Auriault C,Damonneville M,Joseph M,Capron M,Verwaerde C,Billaut P,Capron A

    更新日期:1985-12-01 00:00:00

  • Polyreactive autoantibodies to negatively charged epitopes following Trypanosoma cruzi infection.

    abstract::During the course of many human autoimmune diseases, antibodies which recognize negatively charged epitopes on self antigens are detected. Trypanosoma cruzi, an intracellular protozoan parasite capable of infecting a wide variety of vertebrates, is the cause of Chagas disease in humans. Infection with the parasite fre...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830221204

    authors: Kahn S,Kahn M,Eisen H

    更新日期:1992-12-01 00:00:00

  • CD4⁺ T-cell immunity in the female genital tract is critically dependent on local mucosal immunization.

    abstract::Immunizations via the i.n. and intravaginal (ivag) routes effectively generate strong genital tract antibody-mediated immunity. To what extent the same is true for T-cell responses is incompletely known. Therefore, we set out to investigate optimal conditions for stimulation of genital tract CD4(+) T-cell responses, ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201041297

    authors: Marks E,Helgeby A,Andersson JO,Schön K,Lycke NY

    更新日期:2011-09-01 00:00:00