Abstract:
:The magnitude and quality of T cell responses generated when Ag is targeted to receptors on DC is influenced by both the specific receptor targeted and its distribution among DC subsets. Here we examine the targeting of the model Ag OVA to potential DC targets, including CD11c, CD205, MHC class II, CD40, TLR2 and FcgammaRII/III, using a panel of (Fab' x OVA) conjugates. In vitro studies identified CD11c, CD205 and MHC class II as superior and comparably effective immunotargets for the delivery of OVA to APC for presentation to T cells. In vivo studies, however, showed a marked advantage of targeting Ag to CD11c for both CD4 (OT-II) and CD8 (OT-I) responses, with robust stimulation after a single, low dose (equivalent to 0.5 microg OVA); in contrast, (anti-CD205 x OVA) and (anti-MHC class II x OVA) resulted in markedly less proliferation of both OT-I and OT-II cells. Biodistribution and immunohistochemical studies suggest that the exceptional ability of CD11c to capture Ag in lymphoid tissues may, at least partially, explain its ability to promote T cell responses. These results suggest that targeting antigen via CD11c offers a previously unappreciated strategy for vaccine development which, unlike most targets, delivers robust responses of both CD4 and CD8 T cells.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Castro FV,Tutt AL,White AL,Teeling JL,James S,French RR,Glennie MJdoi
10.1002/eji.200838302subject
Has Abstractpub_date
2008-08-01 00:00:00pages
2263-73issue
8eissn
0014-2980issn
1521-4141journal_volume
38pub_type
杂志文章abstract::For long-term attack on tumor cells in patients with prostate cancer, induction of cytolytic T cells is desirable. Several lineage-specific target proteins are known and algorithms have identified candidate MHC class I-binding peptides, particularly for HLA-A*0201. We have designed tolerance-breaking DNA fusion vaccin...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201141518
更新日期:2011-08-01 00:00:00
abstract::The effect of cyclosporin A (CsA) on the delayed-type hypersensitivity (DTH) elicited in mice by sheep red blood cells was investigated. Evidence is presented that a single injection of CsA adversely affects the inflammatory reaction. Sensitized T lymphocytes initiate the DTH reaction by their recruiting activity on p...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830140407
更新日期:1984-04-01 00:00:00
abstract::A monoclonal antibody, B20.1, was generated by fusing spleen cells from a Lou rat immunized with a soluble alpha/beta T cell receptor (TcR; V alpha 2/V beta 2) to mouse myeloma cells. Analysis of a panel of V alpha 2 mRNA-expressing T cell lines, hybridomas and transfectants revealed that the B20.1 antibody was specif...
journal_title:European journal of immunology
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abstract::Similarities between the physical structures of avian and mammalian major histocompatibility complex (MHC) class I glycoproteins have been proposed based on comparative alignment of their amino acid sequences. To investigate the physical structure of the chicken class I glycoprotein, we cloned the cDNA representing th...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830250740
更新日期:1995-07-01 00:00:00
abstract::The role of CD8(+) T cells in the development of allergic airway disease is controversial. On the one hand, CD8(+) T cells are known to inhibit the development of airway hyperreactivity (AHR) in murine models of asthma. In humans, IL-10-producing CD8(+) T cells were shown to act as regulatory cells, inhibiting both pr...
journal_title:European journal of immunology
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doi:10.1002/eji.200324623
更新日期:2004-07-01 00:00:00
abstract::The concept that naive CD4+ and CD8+ T cells require co-stimulatory signals for activation and proliferation is well documented. Less clear is the need for co-stimulation during the effector phase of the T cell response. Here we examined the influence of B7-1 (CD80) during the effector phase of an autoimmune response ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199803)28:03<949::AID-IMMU
更新日期:1998-03-01 00:00:00
abstract::A method is described for radiolabeling polyanionic macromolecules by the formation of an electrostatic complex with a radioiodinated tyramine conjugated DEAE-dextran. Data is presented on the use of this technique for the detection and quantitation of immunospecific binding of polynitrophenylated proteins, deoxyribon...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830050604
更新日期:1976-06-01 00:00:00
abstract::Once generated during an infection, memory CD8+ T cells can provide long-lasting protection against reinfection with an intracellular pathogen, but the longevity of this defense depends on the ability of these pathogen-specific memory cells to be maintained. It is generally believed that the bone marrow plays an impor...
journal_title:European journal of immunology
pub_type: 评论,杂志文章
doi:10.1002/eji.201747249
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abstract::IL-23, a proximal regulator of IL-17, may be a major driving force in the induction of autoimmune inflammation. We have used a model of subdiabetogenic treatment with multiple low doses of streptozotocin (MLD-STZ; 4 x 40 mg/kg body weight) in male C57BL/6 mice to study the effect of IL-23 on immune-mediated beta cell ...
journal_title:European journal of immunology
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更新日期:2006-01-01 00:00:00
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journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(2000)30:8<2290::AID-IMMU2290>3.0
更新日期:2000-08-01 00:00:00
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
更新日期:1987-12-01 00:00:00
abstract::The activity of granzyme B, a main effector molecule of cytotoxic T lymphocytes (CTL) and natural killer cells, is regulated by the human intracellular serpin proteinase inhibitor 9 (PI9). This inhibitor is particularly expressed by CTL and dendritic cells, in which it serves to protect these cells against endogenous ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200425949
更新日期:2005-04-01 00:00:00
abstract::In hematopoietic stem cell transplantation (HSCT), when no HLA full-matched donor is available, alternative donors could include one HLA-mismatched donor. Recently, the low expressed HLA-C alleles have been identified as permissive mismatches for the best donor choice. Concerning HLA-A, the degree of variability of ex...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201545927
更新日期:2015-12-01 00:00:00
abstract::IL-10 is a potent anti-inflammatory molecule, which regulates TNF-alpha at multiple levels. We investigated whether IL-10 also modulated the activity of the TNF-alpha-converting enzyme (TACE). Using an ex vivo fluorogenic assay we observed that LPS rapidly induced TACE activity in monocytes coinciding with release of ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200737821
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abstract::Recurrent respiratory tract infections (RRTIs) are the first leading cause of community- and nosocomial-acquired infections. Antibiotics remain the mainstay of treatment, enhancing the potential to develop antibiotic resistances. Therefore, the development of new alternative approaches to prevent and treat RRTIs is hi...
journal_title:European journal of immunology
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doi:10.1002/eji.201747024
更新日期:2018-01-01 00:00:00
abstract::The induction of B cell tolerance to 2,4-dinitrophenyl conjugates of polysaccharide antigens (levan or dextran) was studied in mice primed with keyhole limpet hemocyanin (KLH) or 2,4,6-trinitrophenylated KLH. The relationship of the epitope density of the tolerogen with avidity of B cell receptors (as judged indirectl...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830060910
更新日期:1976-09-01 00:00:00
abstract::Follicular helper T (Tfh) cells provide crucial help to germinal center B (GCB) cells for proper antibody production, and a specialized subset of regulatory T cells, follicular regulatory T (Tfr) cells, modulate this process. However, Tfr-cell function in the GC is not well understood. Here, we define Tfr cells as a C...
journal_title:European journal of immunology
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doi:10.1002/eji.201546094
更新日期:2016-05-01 00:00:00
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
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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abstract::After ingestion, oral antigens distribute systemically and provoke T cell stimulation outside the gastrointestinal tract. Within the liver, scavenger liver sinusoidal endothelial cells (LSEC) eliminate blood-borne antigens and induce T cell tolerance. Here we investigated whether LSEC contribute to oral tolerance. Ora...
journal_title:European journal of immunology
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更新日期:2005-10-01 00:00:00
abstract::Stimulation of T cells via the T cell receptor (TCR) leads to an increase intracellular in free Ca2+ levels ([Ca2+]i) and the activation of the MAP kinase signaling pathway. This study analyzes for the first time Ca2+ fluxes in naive cytotoxic T cells stimulated with full agonists, partial agonists, or antagonists. Fo...
journal_title:European journal of immunology
pub_type: 杂志文章
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更新日期:1997-12-01 00:00:00
abstract::In the lymphoid tissues, adaptive immune responses are initiated by the interaction of interdigitating dendritic cells (IDC) with naive T cells. To understand this interplay better, we used mature Langerhans cells (mLC), migrating from human epidermis, as the correlate of IDC ex vivo to evaluate the different effects ...
journal_title:European journal of immunology
pub_type: 杂志文章
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journal_title:European journal of immunology
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abstract::Stimulation of human peripheral blood lymphocytes via T cell receptor/CD3 complex resulted in a bimodal activation of protein kinase(s) C (PKC). Within 10 min of stimulation PKC-alpha was translocated to, and thus activated in, the plasma membranes of human lymphocytes, followed by a fast dissociation of this isotype ...
journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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abstract::Auto-reactive T cells present in healthy subjects remain in a state of unresponsiveness, but may trigger autoimmunity under various situations. Although myelin oligodendrocyte glycoprotein (MOG) is a potential target antigen in multiple sclerosis (MS), MOG-reactive T cell responses are present in the blood of both hea...
journal_title:European journal of immunology
pub_type: 杂志文章
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更新日期:2001-10-01 00:00:00
abstract::One of the clear paradoxes in tumor immunology is the fact that cross-presentation of cell-associated tumor antigens to CD8(+) T cells is efficient, yet CTL generation is weak, and tumors continue to grow. We examined, for the first time whether this may be due to alterations in the phenotype or function of cross-pres...
journal_title:European journal of immunology
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