A T-cell epitope on NS3 non-structural protein enhances the B and T cell responses elicited by dendrimeric constructions against CSFV in domestic pigs

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.

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An Arthritis-Suppressive and Treg Cell-Inducing CD4+ T Cell Epitope Is Functional in the Context of HLA-Restricted T Cell Responses

Arthritis & Rheumatology ◽

10.1002/art.39444 ◽

2016 ◽

Vol 68 (3) ◽

pp. 639-647 ◽

Cited By ~ 13

Author(s):

Charlotte de Wolf ◽

Ruurd van der Zee ◽

Ineke den Braber ◽

Tibor Glant ◽

Bernard Maillère ◽

...

Keyword(s):

T Cell ◽

Treg Cell ◽

Cell Epitope ◽

T Cell Responses ◽

Cd4 T Cell ◽

T Cell Epitope ◽

Cell Responses

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A systematic, unbiased mapping of CD8+ and CD4+ T cell epitopes in Yellow Fever vaccinees

10.1101/2020.03.28.012468 ◽

2020 ◽

Cited By ~ 1

Author(s):

Anette Stryhn ◽

Michael Kongsgaard ◽

Michael Rasmussen ◽

Mikkel Nors Harndahl ◽

Thomas Østerbye ◽

...

Keyword(s):

T Cell ◽

Yellow Fever ◽

Cell Epitope ◽

T Cell Responses ◽

Hla Class I ◽

Class I ◽

T Cell Epitope ◽

T Cell Epitopes ◽

Cell Responses ◽

Epitope Discovery

1.AbstractExamining CD8+ and CD4+ T cell responses after primary Yellow Fever vaccination in a cohort of 210 volunteers, we have identified and tetramer-validated 92 CD8+ and 50 CD4+ T cell epitopes, many inducing strong and prevalent (i.e. immunodominant) T cell responses. Restricted by 40 and 14 HLA-class I and II allotypes, respectively, these responses have wide population coverage and might be of considerable academic, diagnostic and therapeutic interest. The broad coverage of epitopes and HLA overcame the otherwise confounding effects of HLA diversity and non-HLA background providing the first evidence of T cell immunodomination in humans. Also, double-staining of CD4+ T cells with tetramers representing the same HLA-binding core, albeit with different flanking regions, demonstrated an extensive diversification of the specificities of many CD4+ T cell responses. We suggest that this could reduce the risk of pathogen escape, and that multi-tetramer staining is required to reveal the true magnitude and diversity of CD4+ T cell responses. Our T cell epitope discovery approach uses a combination of 1) overlapping peptides representing the entire Yellow Fever virus proteome to search for peptides containing CD4+ and/or CD8+ T cell epitopes, 2) predictors of peptide-HLA binding to suggest epitopes and their restricting HLA allotypes, 3) generation of peptide-HLA tetramers to identify T cell epitopes, and 4) analysis of ex vivo T cell responses to validate the same. This approach is systematic, exhaustive, and can be done in any individual of any HLA haplotype. It is all-inclusive in the sense that it includes all protein antigens and peptide epitopes, and encompasses both CD4+ and CD8+ T cell epitopes. It is efficient and, importantly, reduces the false discovery rate. The unbiased nature of the T cell epitope discovery approach presented here should support the refinement of future peptide-HLA class I and II predictors and tetramer technologies, which eventually should cover all HLA class I and II isotypes. We believe that future investigations of emerging pathogens (e.g. SARS-CoV-2) should include population-wide T cell epitope discovery using blood samples from patients, convalescents and/or long-term survivors, who might all hold important information on T cell epitopes and responses.

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A promiscuous T cell epitope-based HIV vaccine providing redundant population coverage of the HLA class II elicits broad, polyfunctional T cell responses in nonhuman primates

Vaccine ◽

10.1016/j.vaccine.2021.11.076 ◽

2021 ◽

Author(s):

Susan Pereira Ribeiro ◽

Vania Gomes De Moura Mattaraia ◽

Rafael Ribeiro Almeida ◽

Elizabeth Juliana Ghiuro Valentine ◽

Natiely Silva Sales ◽

...

Keyword(s):

T Cell ◽

Nonhuman Primates ◽

Cell Epitope ◽

T Cell Responses ◽

Class Ii ◽

Hla Class Ii ◽

Hiv Vaccine ◽

T Cell Epitope ◽

Population Coverage ◽

Cell Responses

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

Genome Medicine ◽

10.1186/s13073-021-00910-1 ◽

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.

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The same well-characterized T cell epitope SIINFEKL expressed in the context of a cytoplasmic or secreted protein in BCG induces different CD8+ T cell responses

Immunology Letters ◽

10.1016/j.imlet.2009.12.004 ◽

2010 ◽

Vol 130 (1-2) ◽

pp. 36-42 ◽

Cited By ~ 9

Author(s):

Paul D. Hulseberg ◽

Alla Zozulya ◽

Hamlet H. Chu ◽

James A. Triccas ◽

Zsuzsanna Fabry ◽

...

Keyword(s):

T Cell ◽

Cell Epitope ◽

T Cell Responses ◽

Cd8 T Cell ◽

Secreted Protein ◽

T Cell Epitope ◽

Cell Responses

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T Cell Epitope Mapping of JC Polyoma Virus-Encoded Proteome Reveals Reduced T Cell Responses in HLA-DRB1*04:01+ Donors

Journal of Virology ◽

10.1128/jvi.02803-12 ◽

2013 ◽

Vol 87 (6) ◽

pp. 3393-3408 ◽

Cited By ~ 17

Author(s):

I. Jelcic ◽

L. Aly ◽

T. M. C. Binder ◽

I. Jelcic ◽

S. Bofill-Mas ◽

...

Keyword(s):

T Cell ◽

Epitope Mapping ◽

Cell Epitope ◽

T Cell Responses ◽

Polyoma Virus ◽

T Cell Epitope ◽

Cell Responses

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Polymerisation of a T Cell Epitope with an Immunostimulatory C3d Peptide Sequence Enhances Antigen Specific T Cell Responses

International Journal of Peptide Research and Therapeutics ◽

10.1007/s10989-013-9343-2 ◽

2013 ◽

Vol 19 (1) ◽

pp. 81-91

Author(s):

Neil M. O’Brien-Simpson ◽

Troy J. Attard ◽

Baihui Zheng ◽

Katrina A. Walsh ◽

Eric C. Reynolds

Keyword(s):

T Cell ◽

Cell Epitope ◽

T Cell Responses ◽

Peptide Sequence ◽

T Cell Epitope ◽

Cell Responses

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A transplantable tumor model allowing investigation of NY-BR-1-specific T cell responses in HLA-DRB1*0401 transgenic mice

BMC Cancer ◽

10.1186/s12885-019-6102-6 ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Krishna Das ◽

David Eisel ◽

Mathias Vormehr ◽

Karin Müller-Decker ◽

Adriane Hommertgen ◽

...

Keyword(s):

Breast Cancer ◽

T Cells ◽

T Cell ◽

Cell Line ◽

In Silico ◽

Cell Epitope ◽

Tumor Model ◽

T Cell Responses ◽

T Cell Epitope ◽

Cell Responses

Abstract Background NY-BR-1 has been described as a breast cancer associated differentiation antigen with intrinsic immunogenicity giving rise to endogenous T and B cell responses. The current study presents the first murine tumor model allowing functional investigation of NY-BR-1-specific immune responses in vivo. Methods A NY-BR-1 expressing tumor model was established in DR4tg mice based on heterotopic transplantation of stable transfectant clones derived from the murine H2 compatible breast cancer cell line EO771. Composition and phenotype of tumor infiltrating immune cells were analyzed by qPCR and FACS. MHC I binding affinity of candidate CTL epitopes predicted in silico was determined by FACS using the mutant cell line RMA-S. Frequencies of NY-BR-1 specific CTLs among splenocytes of immunized mice were quantified by FACS with an epitope loaded Db-dextramer. Functional CTL activity was determined by IFNγ catch or IFNγ ELISpot assays and statistical analysis was done applying the Mann Whitney test. Tumor protection experiments were performed by immunization of DR4tg mice with replication deficient recombinant adenovirus followed by s.c. challenge with NY-BR-1 expressing breast cancer cells. Results Our results show spontaneous accumulation of CD8+ T cells and F4/80+ myeloid cells preferentially in NY-BR-1 expressing tumors. Upon NY-BR-1-specific immunization experiments combined with in silico prediction and in vitro binding assays, the first NY-BR-1-specific H2-Db-restricted T cell epitope could be identified. Consequently, flow cytometric analysis with fluorochrome conjugated multimers showed enhanced frequencies of CD8+ T cells specific for the newly identified epitope in spleens of immunized mice. Moreover, immunization with Ad.NY-BR-1 resulted in partial protection against outgrowth of NY-BR-1 expressing tumors and promoted intratumoral accumulation of macrophages. Conclusion This study introduces the first H2-Db-resctricted CD8+ T cell epitope-specific for the human breast cancer associated tumor antigen NY-BR-1. Our novel, partially humanized tumor model enables investigation of the interplay between HLA-DR4-restricted T cell responses and CTLs within their joint attack of NY-BR-1 expressing tumors.

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