T Cell Epitope Predictions

2020 ◽  
Vol 38 (1) ◽  
pp. 123-145 ◽  
Author(s):  
Bjoern Peters ◽  
Morten Nielsen ◽  
Alessandro Sette
Keyword(s):  
T Cells ◽  
T Cell ◽  
Epitope Mapping ◽  
Cell Epitope ◽  
Cell Types ◽  
The Body ◽  
Cell Immune Response ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Mhc Molecules

Throughout the body, T cells monitor MHC-bound ligands expressed on the surface of essentially all cell types. MHC ligands that trigger a T cell immune response are referred to as T cell epitopes. Identifying such epitopes enables tracking, phenotyping, and stimulating T cells involved in immune responses in infectious disease, allergy, autoimmunity, transplantation, and cancer. The specific T cell epitopes recognized in an individual are determined by genetic factors such as the MHC molecules the individual expresses, in parallel to the individual's environmental exposure history. The complexity and importance of T cell epitope mapping have motivated the development of computational approaches that predict what T cell epitopes are likely to be recognized in a given individual or in a broader population. Such predictions guide experimental epitope mapping studies and enable computational analysis of the immunogenic potential of a given protein sequence region.

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 Computational Identification and Characterization of a Promiscuous T-Cell Epitope on the Extracellular Protein 85B ofMycobacteriumspp. for Peptide-Based Subunit Vaccine Design

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Md. Saddam Hossain ◽  
Abul Kalam Azad ◽  
Parveen Afroz Chowdhury ◽  
Mamoru Wakayama
Keyword(s):  
Molecular Docking ◽  
T Cell ◽  
Cell Epitope ◽  
Docking Simulation ◽  
Vaccine Design ◽  
Extracellular Protein ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Hla Alleles ◽  
Mhc Molecules

Tuberculosis (TB) is a reemerging disease that remains as a leading cause of morbidity and mortality in humans. To identify and characterize a T-cell epitope suitable for vaccine design, we have utilized the Vaxign server to assess all antigenic proteins ofMycobacteriumspp. recorded to date in the Protegen database. We found that the extracellular protein 85B displayed the most robust antigenicity among the proteins identified. Computational tools for identifying T-cell epitopes predicted an epitope, 181-QQFIYAGSLSALLDP-195, that could bind to at least 13 major histocompatibility complexes, revealing the promiscuous nature of the epitope. Molecular docking simulation demonstrated that the epitope could bind to the binding groove of MHC II and MHC I molecules by several hydrogen bonds. Molecular docking analysis further revealed that the epitope had a distinctive binding pattern to all DRB1 and A and B series of MHC molecules and presented almost no polymorphism in its binding site. Moreover, using “Allele Frequency Database,” we checked the frequency of HLA alleles in the worldwide population and found a higher frequency of both class I and II HLA alleles in individuals living in TB-endemic regions. Our results indicate that the identified peptide might be a universal candidate to produce an efficient epitope-based vaccine for TB.

scholarly journals The heme moiety of cytochrome c is an autoreactive Ir gene-restricted T cell epitope.

1988 ◽  
Vol 168 (3) ◽  
pp. 1127-1143 ◽  
Author(s):  
H M Cooper ◽  
G Corradin ◽  
Y Paterson
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Proliferative Response ◽  
Cell Epitope ◽  
Cell Populations ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Cell Clones ◽  
Cyt C

In these studies, we have shown that the heme moiety of cyt c is a dominant T cell epitope that induces a large proliferative response in lymph node T cells derived from SJL and B10.A mice when presented on either unfixed or fixed syngeneic APCs. Not only is this vigorous response observed for cyt c-primed T cell populations but also for populations obtained from naive SJL or B10.A mice. The reactivity to the heme moiety falls under strict MHC restriction, in that it is present only in murine strains bearing either the I-Ak or I-As molecule and can be blocked by antibodies specific for these class II molecules. Therefore, these findings require that the current models describing the nature of T cell epitopes be extended to include nonpeptide molecules. Furthermore, as the heme moiety is ubiquitous throughout the organism, although sequestered within proteins, the existence of heme-reactive T cell populations in unprimed animals provides another example of the existence of self-reactive T cell clones.

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.

Factor VIII Proteins Having a Rationally Modified, Immunodominant T-Cell Epitope Demonstrate Normal Procoagulant Activity, Bind To VWF With High Affinity, and Are Markedly Less Stimulatory To FVIII-Specific Human T Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 574-574 ◽  
Author(s):  
Ruth A. Ettinger ◽  
Eddie A. James ◽  
Komal Puranik ◽  
Arthur R. Thompson ◽  
Dana C. Matthews ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hemophilia A ◽  
Cell Epitope ◽  
Antigen Presenting Cells ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
High Affinity ◽  
Cell Clones ◽  
Antigen Presenting

Abstract Neutralizing anti-factor VIII (FVIII) antibodies, referred to clinically as “inhibitors”, can develop as an alloimmune response in hemophilia A patients receiving FVIII infusions as replacement therapy. Immune Tolerance Induction, consisting of intensive FVIII treatment in an effort to tolerize patients to FVIII, is extraordinarily expensive and not always successful. New approaches to avoid inhibitor development, and to treat patients who develop this deleterious immune response, are needed. Initial stages of inhibitor development include FVIII uptake and processing into peptides by antigen-presenting cells such as dendritic cells (DCs), presentation of FVIII peptides on MHC Class II (HLA) receptors on the cell surface, and recognition of HLA-peptide complexes by one or more circulating T cells. Subsequent signaling through immunological synapses between antigen-presenting cells and T-cell receptors causes proliferation of effector T cells, which secrete cytokines promoting anti-FVIII antibody production. Our laboratory has been identifying T-cell epitopes in FVIII, which are amino acid sequences 11-15 residues long that bind to specific HLA-DR proteins and are in turn recognized by T cells. FVIII 2194-2205 comprises an immunodominant T-cell epitope that binds to HLA-DRB1*01:01. Peptide-MHC binding experiments established that the side chains of amino acid residues F2196, M2199, A2201 and S2204 fit into the HLA-DRB1*01:01 peptide-binding groove, allowing peptides containing this sequence to be presented on the surface of antigen-presenting cells. Fluorescent HLA-DRB1*01:01 tetramers loaded with FVIII2194-2213 were used to stain and isolate FVIII-specific T cells from 3 hemophilia A subjects who had an HLA-DRB1*01:01 allele. These cells were expanded in culture to generate T-cell clones and polyclonal lines that recognize this sequence and proliferate in response to it. Stimulation of clones with FVIII peptides containing systematic alanine substitutions demonstrated that MHC anchor residues F2196 and M2199 are important for the immunogenicity of this T-cell epitope. The clones were then stimulated with FVIII peptides and recombinant FVIII-C2 domain proteins in which F2196 was changed to a series of other residues. The effect of substitutions at M2199 was examined using the ProPred computer prediction program. Three substitutions that significantly reduced T-cell proliferation (F2196A, F2196L, F2196K) or were predicted to do so (M2199A, M2199W, M2199R) were introduced into recombinant, B-domain-deleted (BDD)-FVIII. The present study tests the hypothesis that less immunogenic FVIII proteins having normal FVIII procoagulant activity can be produced through rational modification of T-cell epitopes. The F2196K and M2199A muteins were expressed at levels similar to wild-type (WT)-BDD-FVIII in BHK-M cells and were purified from serum-free BHK-M cell supernatants. Purified CD14-positive monocytes from individuals with the HLA-DRB1*01:01 allele were differentiated into DCs and used for antigen-presentation assays in which 4 hemophilic T-cell clones and 2 polyclonal lines were added to the DCs and stimulated with FVIII2194-2213, WT-FVIII, WT-BDD-FVIII and the BDD-FVIII muteins. One clone proliferated weakly in response to both the WT and mutant proteins, while the remaining 3 clones and 2 lines showed markedly less proliferation in response to the BDD-FVIII muteins. BDD-FVIII-2196K and 2199A had specific activities similar to that of WT-BDD-FVIII (by chromogenic and clotting assays), and surface plasmon resonance confirmed that they retained high-affinity binding to von Willebrand factor. These results provide proof-of-principle for the design of less immunogenic FVIII proteins targeted to specific subsets of hemophilia A patients. Disclosures: Pratt: Bayer, Pfizer, CSL Behring: Research Funding; Puget Sound Blood Center Research Institute: sequence-modified FVIII variants Patents & Royalties.

scholarly journals Mapping of CD4+ T-cell epitopes in bovine leukemia virus from five cattle with differential susceptibilities to bovine leukemia virus disease progression

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Lanlan Bai ◽  
Shin-nosuke Takeshima ◽  
Masaaki Sato ◽  
William C. Davis ◽  
Satoshi Wada ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Progression ◽  
Bovine Leukemia Virus ◽  
Epitope Mapping ◽  
Leukemia Virus ◽  
Cell Epitope ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Japanese Black Cattle ◽  
Disease Resistant

Abstract Background Bovine leukemia virus (BLV), which is closely related to human T-cell leukemia virus, is the etiological agent of enzootic bovine leukosis, a disease characterized by a highly prolonged course involving persistent lymphocytosis and B-cell lymphoma. The bovine major histocompatibility complex class II region plays a key role in the subclinical progression of BLV infection. In this study, we aimed to evaluate the roles of CD4+ T-cell epitopes in disease progression in cattle. Methods We examined five Japanese Black cattle, including three disease-susceptible animals, one disease-resistant animal, and one normal animal, classified according to genotyping of bovine leukocyte antigen (BoLA)-DRB3 and BoLA-DQA1 alleles using polymerase chain reaction sequence-based typing methods. All cattle were inoculated with BLV-infected blood collected from BLV experimentally infected cattle and then subjected to CD4+ T-cell epitope mapping by cell proliferation assays. Results Five Japanese Black cattle were successfully infected with BLV, and CD4+ T-cell epitope mapping was then conducted. Disease-resistant and normal cattle showed low and moderate proviral loads and harbored six or five types of CD4+ T-cell epitopes, respectively. In contrast, the one of three disease-susceptible cattle with the highest proviral load did not harbor CD4+ T-cell epitopes, and two of three other cattle with high proviral loads each had only one epitope. Thus, the CD4+ T-cell epitope repertoire was less frequent in disease-susceptible cattle than in other cattle. Conclusion Although only a few cattle were included in this study, our results showed that CD4+ T-cell epitopes may be associated with BoLA-DRB3-DQA1 haplotypes, which conferred differential susceptibilities to BLV proviral loads. These CD4+ T-cell epitopes could be useful for the design of anti-BLV vaccines targeting disease-susceptible Japanese Black cattle. Further studies of CD4+ T-cell epitopes in other breeds and using larger numbers of cattle with differential susceptibilities are required to confirm these findings.

scholarly journals On the feasibility of mining CD8+ T-cell receptor patterns underlying immunogenic peptide recognition

2017 ◽  
Author(s):  
Nicolas De Neuter ◽  
Wout Bittremieux ◽  
Charlie Beirnaert ◽  
Bart Cuypers ◽  
Aida Mrzic ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Receptors ◽  
Sequence Data ◽  
Cell Epitope ◽  
Cell Receptor ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Cell Receptors ◽  
Mhc Molecules

Abstract:Current T-cell epitope prediction tools are a valuable resource in designing targeted immunogenicity experiments. They typically focus on, and are able to, accurately predict peptide binding and presentation by major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells. However, recognition of the peptide-MHC complex by a T-cell receptor is often not included in these tools. We developed a classification approach based on random forest classifiers to predict recognition of a peptide by a T-cell and discover patterns that contribute to recognition. We considered two approaches to solve this problem: (1) distinguishing between two sets of T-cell receptors that each bind to a known peptide and (2) retrieving T-cell receptors that bind to a given peptide from a large pool of T-cell receptors. Evaluation of the models on two HIV-1, B*08-restricted epitopes reveals good performance and hints towards structural CDR3 features that can determine peptide immunogenicity. These results are of particularly importance as they show that prediction of T-cell epitope and T-cell epitope recognition based on sequence data is a feasible approach. In addition, the validity of our models not only serves as a proof of concept for the prediction of immunogenic T-cell epitopes but also paves the way for more general and high performing models.

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