scholarly journals Swine T-Cells and Specific Antibodies Evoked by Peptide Dendrimers Displaying Different FMDV T-Cell Epitopes

2021 ◽  
Vol 11 ◽  
Author(s):  
Patricia de León ◽  
Rodrigo Cañas-Arranz ◽  
Sira Defaus ◽  
Elisa Torres ◽  
Mar Forner ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cell Epitope ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
B Cell Epitope ◽  
Mouth Disease Virus ◽  
Ifn Γ

Dendrimeric peptide constructs based on a lysine core that comprises both B- and T-cell epitopes of foot-and-mouth disease virus (FMDV) have proven a successful strategy for the development of FMD vaccines. Specifically, B2T dendrimers displaying two copies of the major type O FMDV antigenic B-cell epitope located on the virus capsid [VP1 (140–158)], covalently linked to a heterotypic T-cell epitope from either non-structural protein 3A [3A (21–35)] or 3D [3D (56–70)], named B2T-3A and B2T-3D, respectively, elicit high levels of neutralizing antibodies (nAbs) and IFN-γ-producing cells in pigs. To assess whether the inclusion and orientation of T-3A and T-3D T-cell epitopes in a single molecule could modulate immunogenicity, dendrimers with T epitopes juxtaposed in both possible orientations, i.e., constructs B2TT-3A3D and B2TT-3D3A, were made and tested in pigs. Both dendrimers elicited high nAbs titers that broadly neutralized type O FMDVs, although B2TT-3D3A did not respond to boosting, and induced lower IgGs titers, in particular IgG2, than B2TT-3A3D. Pigs immunized with B2, a control dendrimer displaying two B-cell epitope copies and no T-cell epitope, gave no nABs, confirming T-3A and T-3D as T helper epitopes. The T-3D peptide was found to be an immunodominant, as it produced more IFN-γ expressing cells than T-3A in the in vitro recall assay. Besides, in pigs immunized with the different dendrimeric peptides, CD4+ T-cells were the major subset contributing to IFN-γ expression upon in vitro recall, and depletion of CD4+ cells from PBMCs abolished the production of this cytokine. Most CD4+IFN-γ+ cells showed a memory (CD4+2E3−) and a multifunctional phenotype, as they expressed both IFN-γ and TNF-α, suggesting that the peptides induced a potent Th1 pro-inflammatory response. Furthermore, not only the presence, but also the orientation of T-cell epitopes influenced the T-cell response, as B2TT-3D3A and B2 groups had fewer cells expressing both cytokines. These results help understand how B2T-type dendrimers triggers T-cell populations, highlighting their potential as next-generation FMD vaccines.

scholarly journals In Silico Identification and in Vitro Analysis of B and T-Cell Epitopes of the Black Turtle Bean (Phaseolus Vulgaris L.) Lectin

2018 ◽  
Vol 49 (4) ◽  
pp. 1600-1614 ◽  
Author(s):  
Shudong He ◽  
Jinlong Zhao ◽  
Walid Elfalleh ◽  
Mohamed Jemaà ◽  
Hanju  Sun ◽  
...  
Keyword(s):  
Amino Acids ◽  
T Cell ◽  
Phaseolus Vulgaris ◽  
B Cell ◽  
Cell Epitope ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Phaseolus Vulgaris L ◽  
B Cell Epitopes ◽  
B Cell Epitope

Background/Aims: The incidence of lectin allergic disease is increasing in recent decades, and definitive treatment is still lacking. Identification of B and T-cell epitopes of allergen will be useful in understanding the allergen antibody responses as well as aiding in the development of new diagnostics and therapy regimens for lectin poisoning. In the current study, we mainly addressed these questions. Methods: Three-dimensional structure of the lectin from black turtle bean (Phaseolus vulgaris L.) was modeled using the structural template of Phytohemagglutinin from P. vulgaris (PHA-E, PDB ID: 3wcs.1.A) with high identity. The B and T-cell epitopes were screened and identified by immunoinformatics and subsequently validated by ELISA, lymphocyte proliferation and cytokine profile analyses. Results: Seven potential B-cell epitopes (B1 to B7) were identified by sequence and structure based methods, while three T-cell epitopes (T1 to T3) were identified by the predictions of binding score and inhibitory concentration. The epitope peptides were synthesized. Significant IgE binding capability was found in B-cell epitopes (B2, B5, B6 and B7) and T2 (a cryptic B-cell epitope). T1 and T2 induced significant lymphoproliferation, and the release of IL-4 and IL-5 cytokine confirmed the validity of T-cell epitope prediction. Abundant hydrophobic amino acids were found in B-cell epitope and T-cell epitope regions by amino acid analysis. Positively charged amino acids, such as His residue, might be more favored for B-cell epitope. Conclusion: The present approach can be applied for the identification of epitopes in novel allergen proteins and thus for designing diagnostics and therapies in lectin allergy.

scholarly journals B Epitope Multiplicity and B/T Epitope Orientation Influence Immunogenicity of Foot-and-Mouth Disease Peptide Vaccines

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Esther Blanco ◽  
Carolina Cubillos ◽  
Noelia Moreno ◽  
Juan Bárcena ◽  
Beatriz G. de la Torre ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Neutralizing Antibodies ◽  
Cell Epitope ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
B Cell Epitope ◽  
Foot And Mouth

Synthetic peptides incorporating protective B- and T-cell epitopes are candidates for new safer foot-and-mouth disease (FMD) vaccines. We have reported that dendrimeric peptides including four copies of a B-cell epitope (VP1 136 to 154) linked to a T-cell epitope (3A 21 to 35) of FMD virus (FMDV) elicit potent B- and T-cell specific responses and confer protection to viral challenge, while juxtaposition of these epitopes in a linear peptide induces less efficient responses. To assess the relevance of B-cell epitope multivalency, dendrimers bearing two (B2T) or four (B4T) copies of the B-cell epitope from type O FMDV (a widespread circulating serotype) were tested in CD1 mice and showed that multivalency is advantageous over simple B-T-epitope juxtaposition, resulting in efficient induction of neutralizing antibodies and optimal release of IFNγ. Interestingly, the bivalent B2T construction elicited similar or even better B- and T-cell specific responses than tetravalent B4T. In addition, the presence of the T-cell epitope and its orientation were shown to be critical for the immunogenicity of the linear juxtaposed monovalent peptides analyzed in parallel. Taken together, our results provide useful insights for a more accurate design of FMD subunit vaccines.

scholarly journals Immunogenicity of a Recombinant Influenza Virus Bearing Both the CD4+ and CD8+ T Cell Epitopes of Ovalbumin

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Bruno Garulli ◽  
Giuseppina Di Mario ◽  
Ester Sciaraffia ◽  
Yoshihiro Kawaoka ◽  
Maria R. Castrucci
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Cell Epitope ◽  
Cd8 T Cell ◽  
Influenza Viruses ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Additional Tool

Recombinant influenza viruses that bear the single immunodominant CD8+ T cell epitopeOVA257−264or the CD4+ T cell epitopeOVA323−339of the model antigen ovalbumin (OVA) have been useful tools in immunology. Here, we generated a recombinant influenza virus,WSN-OVAI/II, that bears both OVA-specific CD8+ and CD4+ epitopes on its hemagglutinin molecule. Live and heat-inactivatedWSN-OVAI/IIviruses were efficiently presented by dendritic cellsin vitroto OT-I TCR transgenic CD8+ T cells and OT-II TCR transgenic CD4+ T cells.In vivo,WSN-OVAI/IIvirus was attenuated in virulence, highly immunogenic, and protected mice from B16-OVA tumor challenge in a prophylactic model of vaccination. Thus,WSN-OVAI/IIvirus represents an additional tool, along with OVA TCR transgenic mice, for further studies on T cell responses and may be of value in vaccine design.

scholarly journals Landscape and selection of vaccine epitopes in SARS-CoV-2

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Christof C. Smith ◽  
Kelly S. Olsen ◽  
Kaylee M. Gentry ◽  
Maria Sambade ◽  
Wolfgang Beck ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Epitope ◽  
T Cell Responses ◽  
Sequence Conservation ◽  
Conformational Space ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Cell Responses ◽  
B Cell Epitope

Abstract Background Early in the pandemic, we designed a SARS-CoV-2 peptide vaccine containing epitope regions optimized for concurrent B cell, CD4+ T cell, and CD8+ T cell stimulation. The rationale for this design was to drive both humoral and cellular immunity with high specificity while avoiding undesired effects such as antibody-dependent enhancement (ADE). Methods We explored the set of computationally predicted SARS-CoV-2 HLA-I and HLA-II ligands, examining protein source, concurrent human/murine coverage, and population coverage. Beyond MHC affinity, T cell vaccine candidates were further refined by predicted immunogenicity, sequence conservation, source protein abundance, and coverage of high frequency HLA alleles. B cell epitope regions were chosen from linear epitope mapping studies of convalescent patient serum, followed by filtering for surface accessibility, sequence conservation, spatial localization near functional domains of the spike glycoprotein, and avoidance of glycosylation sites. Results From 58 initial candidates, three B cell epitope regions were identified. From 3730 (MHC-I) and 5045 (MHC-II) candidate ligands, 292 CD8+ and 284 CD4+ T cell epitopes were identified. By combining these B cell and T cell analyses, as well as a manufacturability heuristic, we proposed a set of 22 SARS-CoV-2 vaccine peptides for use in subsequent murine studies. We curated a dataset of ~ 1000 observed T cell epitopes from convalescent COVID-19 patients across eight studies, showing 8/15 recurrent epitope regions to overlap with at least one of our candidate peptides. Of the 22 candidate vaccine peptides, 16 (n = 10 T cell epitope optimized; n = 6 B cell epitope optimized) were manually selected to decrease their degree of sequence overlap and then synthesized. The immunogenicity of the synthesized vaccine peptides was validated using ELISpot and ELISA following murine vaccination. Strong T cell responses were observed in 7/10 T cell epitope optimized peptides following vaccination. Humoral responses were deficient, likely due to the unrestricted conformational space inhabited by linear vaccine peptides. Conclusions Overall, we find our selection process and vaccine formulation to be appropriate for identifying T cell epitopes and eliciting T cell responses against those epitopes. Further studies are needed to optimize prediction and induction of B cell responses, as well as study the protective capacity of predicted T and B cell epitopes.

scholarly journals Immunogenicity of Foot-and-Mouth Disease Virus Dendrimer Peptides: Need for a T-Cell Epitope and Ability to Elicit Heterotypic Responses

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4714
Author(s):  
Rodrigo Cañas-Arranz ◽  
Patricia de León ◽  
Sira Defaus ◽  
Elisa Torres ◽  
Mar Forner ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Epitope ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Vaccine Platform ◽  
Mouth Disease Virus ◽  
Foot And Mouth

An approach based on a dendrimer display of B- and T-cell epitopes relevant for antibody induction has been shown to be effective as a foot-and-mouth disease (FMD) vaccine. B2T dendrimers combining two copies of the major FMD virus (FMDV) type O B-cell epitope (capsid proteinVP1 (140–158)) covalently linked to a heterotypic T-cell epitope from non-structural protein 3A (21–35), henceforth B2T-3A, has previously been shown to elicit high neutralizing antibody (nAb) titers and IFN-γ-producing cells in both mice and pigs. Here, we provide evidence that the B- and T-cell epitopes need to be tethered to a single molecular platform for successful T-cell help, leading to efficient nAb induction in mice. In addition, mice immunized with a non-covalent mixture of B2T-3A dendrimers containing the B-cell epitopes of FMDV types O and C induced similarly high nAb levels against both serotypes, opening the way for a multivalent vaccine platform against a variety of serologically different FMDVs. These findings are relevant for the design of vaccine strategies based on B- and T-cell epitope combinations.

scholarly journals Vaccination With a FAT1-Derived B Cell Epitope Combined With Tumor-Specific B and T Cell Epitopes Elicits Additive Protection in Cancer Mouse Models

2018 ◽  
Vol 8 ◽  
Author(s):  
Alberto Grandi ◽  
Laura Fantappiè ◽  
Carmela Irene ◽  
Silvia Valensin ◽  
Michele Tomasi ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Mouse Models ◽  
Cell Epitope ◽  
T Cell Epitopes ◽  
B Cell Epitope

Cultured Human B Cell APCs Expanded Using Il-4 and CD40 Ligand Preferentially Promote a Type 2 T Cell Response to Alloimmune Stimulation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2668-2668
Author(s):  
Abdul Tawab ◽  
Yoshiyuki Takahashi ◽  
Childs Richard ◽  
Kurlander J. Roger
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Response ◽  
Cd40 Ligand ◽  
T Cell Response ◽  
Ifn Γ

Abstract In vitro stimulation of human peripheral blood B cells with recombinant IL-4 and CD40 ligand (CD40L) markedly increases their expression of MHC and costimulatory molecules, thus enhancing antigenic peptide presentation to T cells. Because these cells proliferate extensively in vitro (unlike monocytes or dendritic cells), they represent a promising and convenient reagent for the generation and maintenance of antigen-specific T cells for use in a variety of experimental or therapeutic settings. However, the impact of this type of B cell APC on cytokine production by responder T cells has hitherto not been examined. To address this issue, we stimulated normal human T cells with either allogeneic B cells (generated in vitro) or with MNCs obtained from the same donor. After 7 days, T cells were washed and re-challenged with the same APCs. The resulting alloreactive cytokine response was measured using quantitative ELISPOT methods and expressed as the frequencies of IFN-γ, IL-4, and IL-5 producing cells per thousand responder cells added. B cell- and MNC-primed cell lines both produced vigorous lymphokine responses, but B cell-stimulated T cells consistently produced more IL-5 spots (mean of 265 vs. 98/1000 responders, p<0.002) and fewer IFN-γ spots (163 vs 386/1000 cells, p<0.005) than MNC-stimulated cells. Further, the ratio of IFN-γ to IL-5 spots was almost ten-fold lower in B cell-stimulated cultures compared to MNC-induced cultures (0.67 vs. 5.2, p<0.001). ELISPOT studies assessing the ratio of IFN-γ to IL-4 spots and ELISA assays comparing IFN-γ and IL-5 levels from culture supernatants demonstrated the same pattern of marked type 2 skewing by B cells. This pattern was unaffected by the presence of anti-IL-4 antibody suggesting type 2 skewing was not mediated by IL-4. Cytokine skewing produced by B cells or MNC could be partially reversed by swapping MNC and B cells during re-stimulation on day 7, but this plasticity was markedly reduced after 3 (weekly) cycles of B cell or MNC re-stimulation in vitro. Type 2 skewing by B cells was enhanced when monocytes were removed from responder T cell populations by either depleting CD14+ positive cells or by positive selection of T cells prior to stimulation. In contrast, type 2 polarization could be prevented using recombinant IL-12. Not all cells of B-cell origin share the same propensity to type 2 skewing observed with IL-4/CD40L-stimulated B cells; under identical conditions, EBV-transformed B cells stimulated alloimmune T cells to produce a strong type 1 cytokine response comparable to that produced by MNCs. In summary, IL-4/CD40L-stimulated B cells strongly promote a type 2 T cell response during primary alloimmune challenge; this skewing can become fixed after repeated B cell stimulation. Investigators using these cells as APC should be aware of this potential phenomenon, particularly during primary T cell responses. It is also important to consider the factors described above that may exacerbate or ameliorate this effect.

P4-385 Alzheimer's epitope vaccine based on the dominant B cell epitope of Aβ and padre, a foreign T cell epitope

2004 ◽  
Vol 25 ◽  
pp. S584
Author(s):  
Michael G. Agadjanyan ◽  
Irina Petrushina ◽  
Anahit Ghochikyan ◽  
Vitaly Vasilevko ◽  
Nina Movsesyan ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Epitope ◽  
T Cell Epitope ◽  
Epitope Vaccine ◽  
B Cell Epitope

Peptides containing a dominant T-cell epitope from red cell band 3 have in vivo immunomodulatory properties in NZB mice with autoimmune hemolytic anemia

Blood ◽  
2003 ◽  
Vol 102 (10) ◽  
pp. 3800-3806 ◽  
Author(s):  
Chia-Rui Shen ◽  
Abdel-Rahman Youssef ◽  
Anne Devine ◽  
Laura Bowie ◽  
Andrew M. Hall ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Cell Epitope ◽  
Band 3 ◽  
T Cell Epitope ◽  
Helper Epitope

Abstract The major target of the pathogenic red blood cell (RBC) autoantibodies in New Zealand black (NZB) mice is the anion channel protein band 3, and CD4+ T cells from NZB mice respond to band 3. Here, we demonstrate that a band 3 peptide 861-875, which is the predominant sequence recognized by NZB T cells in vitro, bears a dominant helper epitope able to modulate the autoimmune hemolyic anemia in vivo. The development of RBC-bound autoantibodies and anemia was accelerated in NZB mice injected with peptide 861-874, which is relatively insoluble, and inhalation of the peptide primed T cells for both peptide 861-874 and band 3 responses. By contrast, inhalation of a soluble analog (Glu861, Lys875) of peptide 861-874 deviated the autoimmune response toward a T helper-2 (Th2) profile, with marked increases in the ratio of interleukin-4 to interferon-γ produced by splenic T cells responding in vitro to either peptide 861-874 or band 3. Moreover, in mice that had received such treatment, the proportion of RBC-bound immunoglobulin G (IgG) molecules that were of the Th2-associated IgG1 isotype was also increased, and anemia was less severe. It is concluded that NZB autoimmune hemolytic anemia is helper dependent and that nasal administration of different peptides containing the dominant T-cell epitope can have potentially detrimental or beneficial effects on the disease. (Blood. 2003; 102:3800-3806)

scholarly journals Identification of an HLA-A*0201-Restricted T-Cell Epitope on the MPT51 Protein, a Major Secreted Protein Derived from Mycobacterium tuberculosis, by MPT51 Overlapping Peptide Screening

2008 ◽  
Vol 76 (4) ◽  
pp. 1565-1571 ◽  
Author(s):  
Taiki Aoshi ◽  
Toshi Nagata ◽  
Mina Suzuki ◽  
Masato Uchijima ◽  
Dai Hashimoto ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Flow Cytometric Analysis ◽  
Cell Epitope ◽  
T Cell Epitope ◽  
Computer Algorithms ◽  
Dna Encoding ◽  
Color Flow ◽  
Ifn Γ

ABSTRACT CD8+ T cells play a pivotal role in protection against Mycobacterium tuberculosis infection. We identified a novel HLA-A*0201-restricted CD8+ T-cell epitope on a dominant secreted antigen of M. tuberculosis, MPT51, in HLA-A*0201 transgenic HHD mice. HHD mice were immunized with plasmid DNA encoding MPT51 with gene gun bombardment, and gamma interferon (IFN-γ) production by the immune splenocytes was analyzed. In response to overlapping synthetic peptides covering the mature MPT51 sequence, the splenocytes were stimulated to produce IFN-γ by only one peptide, p51-70. Three-color flow cytometric analysis of intracellular IFN-γ and cell surface CD4 and CD8 staining revealed that the MPT51 p51-70 peptide contains an immunodominant CD8+ T-cell epitope. Further analysis using computer algorithms permitted identification of a bona fide T-cell epitope, p53-62. A major histocompatibility complex class I stabilization assay using T2 cells confirmed that this epitope binds to HLA-A*0201. The T cells were capable of lysing MPT51 p53-62 peptide-pulsed T2 cells. In addition, MPT51 p53-62-specific memory CD8+ T cells were found in tuberculin skin test-positive HLA-A*0201+ healthy individuals. Use of this HLA-A*0201-restricted CD8+ T-cell epitope for analysis of the role of MPT51-specific T cells in M. tuberculosis infection and for design of vaccines against tuberculosis is feasible.

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