Characterization of novel HLA-DR11-restricted HCV epitopes reveals both qualitative and quantitative differences in HCV-specific CD4+ T cell responses in chronically infected and non-viremic patients.

Abstract:

:The CD4+ T cell response is of critical importance in determining the fate of many viral infections. Clearance of HCV has a strong association with the MHC class II antigen HLA-DR11 suggesting a key role for CD4+ T cells. We used an epitope-prediction program to identify multiple novel HLA-DR11-restricted epitopes derived from several HCV proteins. These epitopes then allowed us to explore the qualitative and quantitative aspects of specific CD4+ T cell responses in HLA-DR11+ patients. Irrespective of the time since viral clearance, all the non-viremic patients recognized four epitopes with a high frequency of IFN-gamma-producing memory CD4+ T cells. There appeared to be two subpopulations of memory cells, immediate "effector" memory cells (Th1 phenotype) and resting "central" memory cells (Th1/0). Chronically infected patients revealed an almost complete absence of HCV epitope-specific IFN-gamma-producing T cells. However, three of these epitopes induced IL-10 production (down-regulatory) raising the question as to whether these cells play a role in viral persistence. The frequency and phenotype of memory cells is likely to reflect the magnitude of the initial immune response, and suggests that a high frequency of IFN-gamma-secreting CD4+ T cells to multiple epitopes are important in clearance of HCV.

journal_name

Eur J Immunol

authors

Godkin A,Jeanguet N,Thursz M,Openshaw P,Thomas H

doi

10.1002/1521-4141(200105)31:5<1438::AID-IMMU1438>3

keywords:

subject

Has Abstract

pub_date

2001-05-01 00:00:00

pages

1438-46

issue

5

eissn

0014-2980

issn

1521-4141

journal_volume

31

pub_type

杂志文章
  • Involvement of specific Lyt-2+ T cells in the immunological control of experimentally induced murine cutaneous leishmaniasis.

    abstract::The involvement of Lyt-2+ T cells in the immunological control of cutaneous leishmaniasis was assessed by studying the course of the disease in mice in which the number of these cells was reduced by treatment with anti-Lyt-2 monoclonal antibody (mAb). Administration of anti-Lyt-2 mAb exacerbated Leishmania major-induc...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830171007

    authors: Titus RG,Milon G,Marchal G,Vassalli P,Cerottini JC,Louis JA

    更新日期:1987-10-01 00:00:00

  • Mitogen-activated protein kinase and activator protein-1 dependent signals are essential for Bacteroides fragilis enterotoxin-induced enteritis.

    abstract::The approximately 20-kDa heat-labile toxin produced by enterotoxigenic Bacteroides fragilis is known to be associated with the development of enteritis. However, the molecular mechanism involved is not yet fully understood. In this study, we assessed whether B. fragilis enterotoxin (BFT)-induced enteritis is related t...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200526321

    authors: Kim JM,Jung HY,Lee JY,Youn J,Lee CH,Kim KH

    更新日期:2005-09-01 00:00:00

  • Increased cyclic AMP levels block interleukin 2-induced protein kinase C substrate phosphorylation but not the mitogenic response.

    abstract::Protein kinase C (PKC) has been implicated in the signaling of a number of cellular responses including activation of T cells. In the present report we have evaluated the effect of increased cAMP levels on PKC activation after stimulation of two distinct receptor systems on normal human T cells. PKC substrate phosphor...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830190622

    authors: Friedrich B,Cantrell DA,Gullberg M

    更新日期:1989-06-01 00:00:00

  • Epratuzumab modulates B-cell signaling without affecting B-cell numbers or B-cell functions in a mouse model with humanized CD22.

    abstract::Treatment of systemic lupus erythematosus patients with epratuzumab (Emab), a humanized monoclonal antibody targeting CD22, leads to moderately reduced B-cell numbers but does not completely deplete B cells. Emab appears to induce immunomodulation of B cells, but the exact mode of action has not been defined. In the p...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201646383

    authors: Özgör L,Brandl C,Shock A,Nitschke L

    更新日期:2016-09-01 00:00:00

  • Abundance of H-2 promiscuous T cells specific for mycobacterial determinants in H-2b/d F1 hybrid mice.

    abstract::A majority of immunodominant epitopes of mycobacterial antigens are known to be recognized by murine T cells in the context of several H-2 haplotypes. In this study, we established the frequency of T cells able to recognize these peptides promiscuously, i.e. in the context of allogeneic antigen-presenting cells, using...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830251009

    authors: Vordermeier HM,Arya A,Harris DP,Moreno C,Ivanyi J

    更新日期:1995-10-01 00:00:00

  • Regulation of immunoglobulin gene transcription by labile repressor factor(s).

    abstract::The cloned human gamma 1 heavy chain gene (HIG1) was scarcely expressed in the stable transformants of a mouse fibroblast line, L cell or a T cell line, EL4, and no gamma 1 heavy chain was produced in these cells. Upon treatment with cycloheximide or other kinds of protein synthesis inhibitors, the transcription of HI...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830170906

    authors: Kitamura D,Maeda H,Araki K,Kudo A,Watanabe T

    更新日期:1987-09-01 00:00:00

  • Fibrinogen-CD11b/CD18 interaction activates the NF-kappa B pathway and delays apoptosis in human neutrophils.

    abstract::The regulation of neutrophil half-life by members of the coagulation cascade is critical for the resolution of the inflammatory response. We have demonstrated that soluble fibrinogen (sFbg) delays human neutrophil (PMN) apoptosis through a mechanism that involves CD11b interactions, and phosphorylation of focal adhesi...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200323512

    authors: Rubel C,Gómez S,Fernández GC,Isturiz MA,Caamaño J,Palermo MS

    更新日期:2003-05-01 00:00:00

  • Binding of lipopeptide to CD14 induces physical proximity of CD14, TLR2 and TLR1.

    abstract::Lipoproteins or lipopeptides (LP) are bacterial cell wall components detected by the innate immune system. For LP, it has been shown that TLR2 is the essential receptor in cellular activation. However, molecular mechanisms of LP recognition are not yet clear. We used a FLAG-labeled derivative of the synthetic lipopept...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200425336

    authors: Manukyan M,Triantafilou K,Triantafilou M,Mackie A,Nilsen N,Espevik T,Wiesmüller KH,Ulmer AJ,Heine H

    更新日期:2005-03-01 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

    doi:10.1002/eji.1830230303

    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

  • The soluble isoform of CTLA-4 as a regulator of T-cell responses.

    abstract::CTLA-4 is a crucial immune regulator that mediates both negative costimulation signals to T cells, and regulatory T (Treg)-cell extrinsic control of effector responses. Here we present evidence supporting a novel mechanism for this extrinsic suppression, executed by the alternatively spliced soluble CTLA-4 isoform (sC...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201242529

    authors: Ward FJ,Dahal LN,Wijesekera SK,Abdul-Jawad SK,Kaewarpai T,Xu H,Vickers MA,Barker RN

    更新日期:2013-05-01 00:00:00

  • Suppression of specific IgM, IgA and IgG responses in mice treated with anti-delta from birth.

    abstract::In contrast to previous studies, we report that heterologous anti-delta antibodies can act as a powerful multi-class humoral immunosuppressant. Primary direct plaque-forming cell (IgM) responses of BALB/c mice injected from birth with a rabbit anti-delta antiserum were reduced to 3% of control levels against a T-depen...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830160816

    authors: Wathen PM,Manning DD

    更新日期:1986-08-01 00:00:00

  • Soluble anti-mu monoclonal antibodies prime resting B cells to secrete immunoglobulins in response to interleukins-4 and -5.

    abstract::Soluble anti-immunoglobulin (Ig) antibodies have been generally found to inhibit Ig secretion in B cells, via largely unknown mechanisms. To investigate this phenomenon further a two-step culture system was used in which B cells are primed for 24-72 h with various soluble monoclonal or polyclonal anti-Ig antibodies: a...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830220629

    authors: Phillips C,Klaus GG

    更新日期:1992-06-01 00:00:00

  • Selective induction of interleukin-1 receptor antagonist and interleukin-8 in human monocytes by normal polyspecific IgG (intravenous immunoglobulin).

    abstract::We have investigated the effects of intravenous immunoglobulin (IVIg), a therapeutic preparation of normal human polyspecific IgG, on the synthesis and release of cytokines by peripheral blood monocytes. IVIg was found to selectively induce gene transcription and secretion of interleukin-1 receptor antagonist (IL-1ra)...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830250521

    authors: Ruiz de Souza V,Carreno MP,Kaveri SV,Ledur A,Sadeghi H,Cavaillon JM,Kazatchkine MD,Haeffner-Cavaillon N

    更新日期:1995-05-01 00:00:00

  • Among naive precursor cell subpopulations only progenitors of memory B cells originate germinal centers.

    abstract::Immunization leads to the generation of both antibody-forming cells (AFC) and memory B cells which are thought to arise in germinal centers within lymphoid follicles. The findings that the precursors to memory B cells reside in the J11Dlo subpopulation of the spleens in non-immune mice and that this subpopulation is d...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830220526

    authors: Linton PJ,Lo D,Lai L,Thorbecke GJ,Klinman NR

    更新日期:1992-05-01 00:00:00

  • Soluble HLA-I-mediated secretion of TGF-beta1 by human NK cells and consequent down-regulation of anti-tumor cytolytic activity.

    abstract::Soluble HLA class I (sHLA-I) molecules can regulate survival of NK cells and their anti-tumor killing activity. Herein, we have analysed whether interaction of sHLA-I with CD8 and/or different isoforms of killer Ig-like receptors (KIR) induced secretion of transforming growth factor (TGF)-beta1. CD8+KIR- NK cell clone...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200939728

    authors: Ghio M,Contini P,Negrini S,Boero S,Musso A,Poggi A

    更新日期:2009-12-01 00:00:00

  • The origin of follicular dendritic cells in the mouse and the mechanism of trapping of immune complexes on them.

    abstract::F1----parental bone marrow chimeras between CBA and B10 mice were used to show that even after 1 year follicular dendritic cells (FDC), also termed dendritic reticular cells, are not derived from bone marrow stem cells. However clusters of cells wrapped in the dendritic processes of FDC, isolated by enzyme digestion o...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830140916

    authors: Humphrey JH,Grennan D,Sundaram V

    更新日期:1984-09-01 00:00:00

  • Dimerization of Fab fragments enables ready screening of phage antibodies that affect hepatocyte growth factor/scatter factor activity on target cells.

    abstract::A number of applications of antibodies in diagnosis and therapy require multivalent reagents either because of the polymeric nature of the antigens or because biological activity depends on an effect on the formation of homodimeric species. Here, we report a procedure for mass screening of phage-derived monomeric anti...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830270307

    authors: Zaccolo M,Griffiths AP,Prospero TD,Winter G,Gherardi E

    更新日期:1997-03-01 00:00:00

  • Flt3 ligand-eGFP-reporter expression characterizes functionally distinct subpopulations of CD150+ long-term repopulating murine hematopoietic stem cells.

    abstract::The pool of hematopoietic stem cells (HSCs) in the bone marrow is a mixture of resting, proliferating, and differentiating cells. Long-term repopulating HSCs (LT-HSC) are routinely enriched as Lin- Sca1+ c-Kit+ CD34- Flt3- CD150+ CD48- cells. The Flt3 ligand (Flt3L) and its receptor Flt3 are important regulators of HS...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201646730

    authors: Tornack J,Kawano Y,Garbi N,Hämmerling GJ,Melchers F,Tsuneto M

    更新日期:2017-09-01 00:00:00

  • The adaptor ASC exacerbates lethal Listeria monocytogenes infection by mediating IL-18 production in an inflammasome-dependent and -independent manner.

    abstract::Listeria monocytogenes induces the formation of inflammasomes and subsequent caspase-1 activation, and the adaptor apoptosis-associated speck-like protein containing a CARD (ASC) is crucial for this response. However, the role of ASC in L. monocytogenes infection in vivo is unclear. In this study, we demonstrate that ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201444673

    authors: Tsuchiya K,Hara H,Fang R,Hernandez-Cuellar E,Sakai S,Daim S,Chen X,Dewamitta SR,Qu H,Mitsuyama M,Kawamura I

    更新日期:2014-12-01 00:00:00

  • Monoclonal gammopathies in aging mu, kappa-transgenic mice: involvement of the B-1 cell lineage.

    abstract::Monoclonal gammopathies (MG) are monoclonal proliferative disorders of B cells at the differentiation stage of Ig production. They can be detected in the serum, either as transient or as persistent homogenous immunoglobulin (H-Ig) components. The exact phenotype, localization, and cell lineage origin of the precursor ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830270943

    authors: van Arkel C,Hopstaken CM,Zurcher C,Bos NA,Kroese FG,Savelkoul HF,Benner R,Radl J

    更新日期:1997-09-01 00:00:00

  • Isolation of antigen-specific T cell clones from nonresponder mice.

    abstract::The mechanisms responsible for major histocompatibility complex (MHC)-linked unresponsiveness are still poorly understood. Here we examine the cellular events that follow when B10. A mice are immunized with cow insulin, an antigen to which they make no apparent immunologic response. Despite the fact that there is no d...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830180122

    authors: Abromson-Leeman S,Laning J,Cantor H,Dorf ME

    更新日期:1988-01-01 00:00:00

  • Anti-inflammatory effects of high-dose IgG on TNF-α-activated human coronary artery endothelial cells.

    abstract::High-dose infusion of IgG (IVIG) is used to treat autoimmune and inflammatory diseases, including Kawasaki disease (KD). Although the immunomodulatory effects of IVIG on blood cells such as macrophages have been well studied, its effects on tissue cells remain unclear. Here, we show that high-dose IgG specifically and...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201242398

    authors: Matsuda A,Morita H,Unno H,Saito H,Matsumoto K,Hirao Y,Munechika K,Abe J

    更新日期:2012-08-01 00:00:00

  • Cytolytic T cell hybridomas. II. Interleukin 2-independent cytolytic variants.

    abstract::Interleukin 2 (IL2)-dependent cytolytic hybrids usually loose IL2 dependence and cytolytic activity concomittantly. Here we describe an exceptional IL2-independent variant which lost IL2 receptor but retained cytolytic activity. When the IL2-independent cytolytic hybrid cells were fused with IL2-dependent cytolytic cl...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830150803

    authors: Haas W,Kisielow P

    更新日期:1985-08-01 00:00:00

  • Taste receptor T1R1/T1R3 promotes the tumoricidal activity of hepatic CD49a+ CD49b- natural killer cells.

    abstract::Natural Killer (NK) cell-based immunotherapy is a promising approach to treat hepatocellular carcinoma (HCC). The mechanisms underlying the regulation of NK cell activity are not completely understood. In this research, we identified the expression of taste receptor type 1 member 1 (T1R1) and taste receptor type 1 mem...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201847688

    authors: Liu S,Xu M,Zhu C,Zhao Q,Zhou F

    更新日期:2018-12-01 00:00:00

  • Role of N-linked glycosylation in expression of E-selectin on human endothelial cells.

    abstract::E-selectin is a cytokine-inducible membrane glycoprotein capable of mediating adhesion of leukocytes to endothelial cells. It is highly glycosylated, containing 11 sites for N-linked glycosylation. N-Glycosylation of E-selectin was analyzed by endoglycosidase treatment. Analysis of immunoprecipitated E-selectin from h...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830250907

    authors: Påhlsson P,Strindhall J,Srinivas U,Lundblad A

    更新日期:1995-09-01 00:00:00

  • Evidence for Th2 cell-mediated suppression of antibody responses in transgenic, beef insulin-tolerant mice.

    abstract::Clonal deletion, anergy and suppression have all been considered mechanisms of immunological tolerance. Although adoptive transfer of immunosuppression has been shown to occur in the periphery, particularly for transplantation tolerance, it has proven difficult to characterize this phenomenon further, due to the lack ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830250917

    authors: Teng YT,Gorczynski RM,Iwasaki S,Williams DB,Hozumi N

    更新日期:1995-09-01 00:00:00

  • Pharmacological inhibition of RORC2 enhances human Th17-Treg stability and function.

    abstract::Inflammatory bowel diseases (IBD) are chronic conditions that result from uncontrolled intestinal inflammation. Pathogenic Th17 cells, characterized by production of IL-17A in the absence of IL-10, are thought to contribute to this inflammation, but in humans, antibody-mediated blockade of IL-17A is an ineffective IBD...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201948435

    authors: Boardman DA,Garcia RV,Ivison SM,Bressler B,Dhar TM,Zhao Q,Levings MK

    更新日期:2020-09-01 00:00:00

  • Urtica dioica agglutinin, a V beta 8.3-specific superantigen, prevents the development of the systemic lupus erythematosus-like pathology of MRL lpr/lpr mice.

    abstract::The V beta 8.3-specific superantigenic lectin Urtica dioica agglutinin (UDA) was used to delete the V beta 8.3+ T cells in MRL lpr/lpr mice. In contrast to the systemic lupus erythematosus-like pathology which progresses with age in the phosphate-buffered saline-injected MRL lpr/lpr controls, UDA-treated animals did n...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830260807

    authors: Musette P,Galelli A,Chabre H,Callard P,Peumans W,Truffa-Bachi P,Kourilsky P,Gachelin G

    更新日期:1996-08-01 00:00:00

  • Arthritis induced with cartilage-specific antibodiesis IL-4-dependent.

    abstract::It is widely believed that IL-4 exerts its influence by profiling the immune response during priming and expansion of immune cells, and thereby modulates the outcome of chronic inflammation. In the present investigation, collagen antibody-induced arthritis (CAIA) was used to delineate the role of IL-4 in a T cell-inde...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200535633

    authors: Nandakumar KS,Holmdahl R

    更新日期:2006-06-01 00:00:00

  • Endothelial expression of PD-L1 and PD-L2 down-regulates CD8+ T cell activation and cytolysis.

    abstract::Interactions between CD8+ T cells and endothelial cells are important in both protective and pathologic immune responses. Endothelial cells regulate the recruitment of CD8+ T cells into tissues, and the activation of CD8+ T cells by antigen presentation and costimulatory signals. PD-L1 and PD-L2 are recently described...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200324270

    authors: Rodig N,Ryan T,Allen JA,Pang H,Grabie N,Chernova T,Greenfield EA,Liang SC,Sharpe AH,Lichtman AH,Freeman GJ

    更新日期:2003-11-01 00:00:00