scholarly journals DNA as an Adjuvant: Capacity of Insect DNA and Synthetic Oligodeoxynucleotides to Augment T Cell Responses to Specific Antigen

1998 ◽  
Vol 187 (7) ◽  
pp. 1145-1150 ◽  
Author(s):  
Siquan Sun ◽  
Hidehiro Kishimoto ◽  
Jonathan Sprent
Keyword(s):  
T Cell ◽  
Specific Antigen ◽  
Cell Receptor ◽  
Soluble Form ◽  
Protein Antigens ◽  
Adjuvant Activity ◽  
Cell Responses ◽  
Cpg Motifs ◽  
Antigen Presenting

How strong adjuvants such as complete Freund's adjuvant (CFA) promote T cell priming to protein antigens in vivo is still unclear. Since the unmethylated CpG motifs in DNA of bacteria and other nonvertebrates are stimulatory for B cells and antigen-presenting cells, the strong adjuvanticity of CFA could be attributed, at least in part, to the presence of dead bacteria, i.e., a source of stimulatory DNA. In support of this possibility, evidence is presented that insect DNA in mineral oil has even stronger adjuvant activity than CFA by a number of parameters. Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs mimic the effects of insect DNA and, even in soluble form, ODNs markedly potentiate clonal expansion of T cell receptor transgenic T cells responding to specific peptide.

scholarly journals CD1: From Molecules to Diseases

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1909 ◽  
Author(s):  
D. Branch Moody ◽  
Sara Suliman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Ex Vivo ◽  
Cell Receptor ◽  
High Genetic Diversity ◽  
Disease States ◽  
New Research ◽  
Antigen Presenting ◽  
Cluster Of Differentiation

The human cluster of differentiation (CD)1 system for antigen display is comprised of four types of antigen-presenting molecules, each with a distinct functional niche: CD1a, CD1b, CD1c, and CD1d. Whereas CD1 proteins were thought solely to influence T-cell responses through display of amphipathic lipids, recent studies emphasize the role of direct contacts between the T-cell receptor and CD1 itself. Moving from molecules to diseases, new research approaches emphasize human CD1-transgenic mouse models and the study of human polyclonal T cells in vivo or ex vivo in disease states. Whereas the high genetic diversity of major histocompatibility complex (MHC)-encoded antigen-presenting molecules provides a major hurdle for designing antigens that activate T cells in all humans, the simple population genetics of the CD1 system offers the prospect of discovering or designing broadly acting immunomodulatory agents.

scholarly journals A Framework to Identify Antigen-Expanded T Cell Receptor Clusters Within Complex Repertoires

2021 ◽  
Vol 12 ◽  
Author(s):  
Valentina Ceglia ◽  
Erin J. Kelley ◽  
Annalee S. Boyle ◽  
Sandra Zurawski ◽  
Heather L. Mead ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Responses ◽  
Cell Receptor ◽  
Antigen Specificity ◽  
Protein Antigens ◽  
Cell Responses ◽  
Tcr Repertoire ◽  
Receptor Clusters ◽  
Theoretical Sensitivity

Common approaches for monitoring T cell responses are limited in their multiplexity and sensitivity. In contrast, deep sequencing of the T Cell Receptor (TCR) repertoire provides a global view that is limited only in terms of theoretical sensitivity due to the depth of available sampling; however, the assignment of antigen specificities within TCR repertoires has become a bottleneck. This study combines antigen-driven expansion, deep TCR sequencing, and a novel analysis framework to show that homologous ‘Clusters of Expanded TCRs (CETs)’ can be confidently identified without cell isolation, and assigned to antigen against a background of non-specific clones. We show that clonotypes within each CET respond to the same epitope, and that protein antigens stimulate multiple CETs reactive to constituent peptides. Finally, we demonstrate the personalized assignment of antigen-specificity to rare clones within fully-diverse uncultured repertoires. The method presented here may be used to monitor T cell responses to vaccination and immunotherapy with high fidelity.

CpG oligonucleotides induce strong humoral but only weak CD4+ T cell responses to protein antigens in rhesus macaques in vivo

Vaccine ◽  
2005 ◽  
Vol 23 (25) ◽  
pp. 3310-3317 ◽  
Author(s):  
Gunther Hartmann ◽  
Anja Marschner ◽  
Pablo Renner Viveros ◽  
Christiane Stahl-Hennig ◽  
Martin Eisenblätter ◽  
...  
Keyword(s):  
T Cell ◽  
Rhesus Macaques ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Protein Antigens ◽  
Cell Responses ◽  
Cpg Oligonucleotides

scholarly journals Induction of Polyomavirus-Specific CD8+T Lymphocytes by Distinct Dendritic Cell Subpopulations

2001 ◽  
Vol 75 (1) ◽  
pp. 544-547 ◽  
Author(s):  
Donald R. Drake ◽  
Mandy L. Shawver ◽  
Annette Hadley ◽  
Eric Butz ◽  
Charles Maliszewski ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cell Epitope ◽  
T Cell Responses ◽  
T Cell Epitope ◽  
Cell Responses ◽  
Cd8 T Lymphocytes ◽  
Cell Subpopulations ◽  
Antigen Presenting

ABSTRACT Dendritic cells are pivotal antigen-presenting cells for generating adaptive T-cell responses. Here, we show that dendritic cells belonging to either the myeloid-related or lymphoid-related subset are permissive for infection by mouse polyomavirus and, when loaded with a peptide corresponding to the immunodominant anti-polyomavirus CD8+T-cell epitope or infected by polyomavirus, are each capable of driving expansion of primary polyomavirus-specific CD8+ T-cell responses in vivo.

scholarly journals Dendritic cells are potent antigen-presenting cells for microbial superantigens.

1992 ◽  
Vol 175 (1) ◽  
pp. 267-273 ◽  
Author(s):  
N Bhardwaj ◽  
S M Friedman ◽  
B C Cole ◽  
A J Nisanian
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Antigen Presenting Cells ◽  
Small Subset ◽  
Cell Functions ◽  
Cell Responses ◽  
Antigen Presenting

Dendritic cells are a small subset of human blood mononuclear cells that are potent stimulators of several T cell functions. Here we show they are 10-50-fold more potent than monocytes or B cells in inducing T cell responses to a panel of superantigens. Furthermore, dendritic cells can present femtomolar concentrations of superantigen to T cells even at numbers where other antigen-presenting cells (APCs) are inactive. Although dendritic cells express very high levels of the major histocompatibility complex products that are required to present superantigens, it is only necessary to pulse these APCs for 1 hour with picomolar levels of one superantigen, staphylococcal enterotoxin B, to maximally activate T cells. Our results suggest that very small amounts of superantigen will be immunogenic in vivo if presented on dendritic cells.

scholarly journals Direct Expansion of Functional CD25+ CD4+ Regulatory T Cells by Antigen-processing Dendritic Cells

2003 ◽  
Vol 198 (2) ◽  
pp. 235-247 ◽  
Author(s):  
Sayuri Yamazaki ◽  
Tomonori Iyoda ◽  
Kristin Tarbell ◽  
Kara Olson ◽  
Klara Velinzon ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd4 T Cells ◽  
Antigen Processing ◽  
Specific Antigen ◽  
Cell Receptor ◽  
Cd4 T Cell

An important pathway for immune tolerance is provided by thymic-derived CD25+ CD4+ T cells that suppress other CD25− autoimmune disease–inducing T cells. The antigen-presenting cell (APC) requirements for the control of CD25+ CD4+ suppressor T cells remain to be identified, hampering their study in experimental and clinical situations. CD25+ CD4+ T cells are classically anergic, unable to proliferate in response to mitogenic antibodies to the T cell receptor complex. We now find that CD25+ CD4+ T cells can proliferate in the absence of added cytokines in culture and in vivo when stimulated by antigen-loaded dendritic cells (DCs), especially mature DCs. With high doses of DCs in culture, CD25+ CD4+ and CD25− CD4+ populations initially proliferate to a comparable extent. With current methods, one third of the antigen-reactive T cell receptor transgenic T cells enter into cycle for an average of three divisions in 3 d. The expansion of CD25+ CD4+ T cells stops by day 5, in the absence or presence of exogenous interleukin (IL)-2, whereas CD25− CD4+ T cells continue to grow. CD25+ CD4+ T cell growth requires DC–T cell contact and is partially dependent upon the production of small amounts of IL-2 by the T cells and B7 costimulation by the DCs. After antigen-specific expansion, the CD25+ CD4+ T cells retain their known surface features and actively suppress CD25− CD4+ T cell proliferation to splenic APCs. DCs also can expand CD25+ CD4+ T cells in the absence of specific antigen but in the presence of exogenous IL-2. In vivo, both steady state and mature antigen-processing DCs induce proliferation of adoptively transferred CD25+ CD4+ T cells. The capacity to expand CD25+ CD4+ T cells provides DCs with an additional mechanism to regulate autoimmunity and other immune responses.

Indirect inhibition of in vivo and in vitro T-cell responses by intravenous immunoglobulins due to impaired antigen presentation

Blood ◽  
2010 ◽  
Vol 115 (9) ◽  
pp. 1727-1734 ◽  
Author(s):  
Éric Aubin ◽  
Réal Lemieux ◽  
Renée Bazin
Keyword(s):  
T Cell ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
T Cell Responses ◽  
Antigen Presenting Cells ◽  
In Vivo Model ◽  
Cell Responses ◽  
Antigen Presenting

Abstract Several clinical studies done with intravenous immunoglobulin (IVIg)–treated autoimmune patients as well as several in vitro studies have revealed that IVIg can reduce polyclonal T-cell activation and modify their cytokine secretion pattern. However, their effect on (auto)antigen-specific T-cell responses has never been addressed directly. In the present work, we used an in vivo model of induction of antigen-specific T-cell responses and an in vitro antigen presentation system to study the effects of IVIg on T-cell responses. The results obtained showed that IVIg inhibited both the in vivo and in vitro antigen-specific T-cell responses but that this effect was the indirect consequence of a reduction in the antigen presentation ability of antigen-presenting cells. The inhibitory effect of IVIg was FcγRIIb-independent, suggesting that IVIg must interfere with activating FcγRs expressed on antigen-presenting cells to reduce their ability to present antigens. Such inhibition of T-cell responses by reducing antigen presentation may therefore contribute to the well-known anti-inflammatory effects of IVIg in autoimmune diseases.

scholarly journals Development of a System To Study CD4+-T-Cell Responses to Transgenic Ovalbumin-Expressing Toxoplasma gondii during Toxoplasmosis

2004 ◽  
Vol 72 (12) ◽  
pp. 7240-7246 ◽  
Author(s):  
Marion Pepper ◽  
Florence Dzierszinski ◽  
Amy Crawford ◽  
Christopher A. Hunter ◽  
David Roos
Keyword(s):  
T Cells ◽  
T Cell ◽  
Toxoplasma Gondii ◽  
T Cell Responses ◽  
Cell Receptor ◽  
In Vivo Studies ◽  
Cell Responses ◽  
Ifn Γ

ABSTRACT The study of the immune response to Toxoplasma gondii has provided numerous insights into the role of T cells in resistance to intracellular infections. However, the complexity of this eukaryote pathogen has made it difficult to characterize immunodominant epitopes that would allow the identification of T cells with a known specificity for parasite antigens. As a consequence, analysis of T-cell responses to T. gondii has been based on characterization of the percentage of T cells that express an activated phenotype during infection and on the ability of these cells to produce cytokines in response to complex mixtures of parasite antigens. In order to study specific CD4+ T cells responses to T. gondii, recombinant parasites that express a truncated ovalbumin (OVA) protein, in either a cytosolic or a secreted form, were engineered. In vitro and in vivo studies reveal that transgenic parasites expressing secreted OVA are able to stimulate T-cell receptor-transgenic OVA-specific CD4+ T cells to proliferate, express an activated phenotype, and produce gamma interferon (IFN-γ). Furthermore, the adoptive transfer of OVA-specific T cells into IFN-γ−/− mice provided enhanced protection against infection with the OVA-transgenic (but not parental) parasites. Together, these studies establish the utility of this transgenic system to study CD4+-T-cell responses during toxoplasmosis.

scholarly journals SpeS: A Novel Superantigen and Its Potential as a Vaccine Adjuvant against Strangles

2020 ◽  
Vol 21 (12) ◽  
pp. 4467
Author(s):  
C. Coral Dominguez-Medina ◽  
Nicola L. Rash ◽  
Sylvain Robillard ◽  
Carl Robinson ◽  
Androulla Efstratiou ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Surface Protein ◽  
Cell Receptor ◽  
Class Ii ◽  
Surface Proteins ◽  
Binding Motif ◽  
Binding Properties ◽  
Antigen Presenting

Bacterial superantigens (sAgs) are powerful activators of the immune response that trigger unspecific T cell responses accompanied by the release of proinflammatory cytokines. Streptococcus equi (S. equi) and Streptococcus zooepidemicus (S. zooepidemicus) produce sAgs that play an important role in their ability to cause disease. Strangles, caused by S. equi, is one of the most common infectious diseases of horses worldwide. Here, we report the identification of a new sAg of S. zooepidemicus, SpeS, and show that mutation of the putative T cell receptor (TCR)-binding motif (YAY to IAY) abrogated TCR-binding, whilst maintaining interaction with major histocompatibility complex (MHC) class II molecules. The fusion of SpeS and SpeSY39I to six S. equi surface proteins using two different peptide linkers was conducted to determine if MHC class II-binding properties were maintained. Proliferation assays, qPCR and flow cytometry analysis showed that SpeSY39I and its fusion proteins induced less mitogenic activity and interferon gamma expression when compared to SpeS, whilst retaining Antigen-Presenting Cell (APC)-binding properties. Our data suggest that SpeSY39I-surface protein fusions could be used to direct vaccine antigens towards antigen-presenting cells in vivo with the potential to enhance antigen presentation and improve immune responses.

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