T cell epitope mapping identifies reactive CD4 T cell epitopes of ixekizumab, but not secukinumab

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.

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T Cell Epitope Predictions

Annual Review of Immunology ◽

10.1146/annurev-immunol-082119-124838 ◽

2020 ◽

Vol 38 (1) ◽

pp. 123-145 ◽

Cited By ~ 29

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.

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CD4 T-Cell Epitope Mapping

Meningococcal Vaccines ◽

10.1385/1-59259-148-5:349 ◽

2003 ◽

pp. 349-360 ◽

Cited By ~ 1

Author(s):

Alexei A. Delvig ◽

John H. Robinson

Keyword(s):

T Cell ◽

Epitope Mapping ◽

Cell Epitope ◽

Cd4 T Cell ◽

T Cell Epitope

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A Proteome-Wide Immunoinformatics Tool to Accelerate T-Cell Epitope Discovery and Vaccine Design in the Context of Emerging Infectious Diseases: An Ethnicity-Oriented Approach

Frontiers in Immunology ◽

10.3389/fimmu.2021.598778 ◽

2021 ◽

Vol 12 ◽

Author(s):

Patricio Oyarzun ◽

Manju Kashyap ◽

Victor Fica ◽

Alexis Salas-Burgos ◽

Faviel F. Gonzalez-Galarza ◽

...

Keyword(s):

T Cell ◽

Infectious Diseases ◽

Immune Responses ◽

Cell Epitope ◽

Emerging Infectious Diseases ◽

Cd4 T Cell ◽

Immune Responsiveness ◽

T Cell Epitope ◽

T Cell Epitopes ◽

Epitope Discovery

Emerging infectious diseases (EIDs) caused by viruses are increasing in frequency, causing a high disease burden and mortality world-wide. The COVID-19 pandemic caused by the novel SARS-like coronavirus (SARS-CoV-2) underscores the need to innovate and accelerate the development of effective vaccination strategies against EIDs. Human leukocyte antigen (HLA) molecules play a central role in the immune system by determining the peptide repertoire displayed to the T-cell compartment. Genetic polymorphisms of the HLA system thus confer a strong variability in vaccine-induced immune responses and may complicate the selection of vaccine candidates, because the distribution and frequencies of HLA alleles are highly variable among different ethnic groups. Herein, we build on the emerging paradigm of rational epitope-based vaccine design, by describing an immunoinformatics tool (Predivac-3.0) for proteome-wide T-cell epitope discovery that accounts for ethnic-level variations in immune responsiveness. Predivac-3.0 implements both CD8+ and CD4+ T-cell epitope predictions based on HLA allele frequencies retrieved from the Allele Frequency Net Database. The tool was thoroughly assessed, proving comparable performances (AUC ~0.9) against four state-of-the-art pan-specific immunoinformatics methods capable of population-level analysis (NetMHCPan-4.0, Pickpocket, PSSMHCPan and SMM), as well as a strong accuracy on proteome-wide T-cell epitope predictions for HIV-specific immune responses in the Japanese population. The utility of the method was investigated for the COVID-19 pandemic, by performing in silico T-cell epitope mapping of the SARS-CoV-2 spike glycoprotein according to the ethnic context of the countries where the ChAdOx1 vaccine is currently initiating phase III clinical trials. Potentially immunodominant CD8+ and CD4+ T-cell epitopes and population coverages were predicted for each population (the Epitope Discovery mode), along with optimized sets of broadly recognized (promiscuous) T-cell epitopes maximizing coverage in the target populations (the Epitope Optimization mode). Population-specific epitope-rich regions (T-cell epitope clusters) were further predicted in protein antigens based on combined criteria of epitope density and population coverage. Overall, we conclude that Predivac-3.0 holds potential to contribute in the understanding of ethnic-level variations of vaccine-induced immune responsiveness and to guide the development of epitope-based next-generation vaccines against emerging pathogens, whose geographic distributions and populations in need of vaccinations are often well-defined for regional epidemics.

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Cytokine patterns of newly identified HEV-specific CD4 T cell epitope

10.1055/s-0039-3402257 ◽

2020 ◽

Author(s):

B Csernalabics ◽

M Smits ◽

K Zoldan ◽

M Panning ◽

C Neumann-Haefelin ◽

...

Keyword(s):

T Cell ◽

Cell Epitope ◽

Cd4 T Cell ◽

T Cell Epitope

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A novel CD4 T-cell epitope described from one of the cervical cancer patients vaccinated with HPV 16 or 18 E7-pulsed dendritic cells

Cancer Immunology Immunotherapy ◽

10.1007/s00262-008-0617-z ◽

2008 ◽

Vol 58 (2) ◽

pp. 309-309

Author(s):

Xuelian Wang ◽

Alessandro D. Santin ◽

Stefania Bellone ◽

Sushil Gupta ◽

Mayumi Nakagawa

Keyword(s):

Cervical Cancer ◽

Dendritic Cells ◽

T Cell ◽

Cancer Patients ◽

Cell Epitope ◽

Cd4 T Cell ◽

T Cell Epitope ◽

Hpv 16

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T-cell-epitope mapping of the idiotypic monoclonal IgG heavy and light chains in multiple myeloma

International Journal of Cancer ◽

10.1002/(sici)1097-0215(19990301)80:5<671::aid-ijc7>3.0.co;2-e ◽

1999 ◽

Vol 80 (5) ◽

pp. 671-680 ◽

Cited By ~ 34

Author(s):

Jan Fagerberg ◽

Qing Yi ◽

Dulceaydee Gigliotti ◽

Ulrika Harmenberg ◽

Ulla Rud�n ◽

...

Keyword(s):

Multiple Myeloma ◽

T Cell ◽

Epitope Mapping ◽

Cell Epitope ◽

Light Chains ◽

T Cell Epitope

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T-cell epitope mapping

Methods ◽

10.1016/s1046-2023(02)00343-2 ◽

2003 ◽

Vol 29 (3) ◽

pp. 211-212 ◽

Cited By ~ 1

Keyword(s):

T Cell ◽

Epitope Mapping ◽

Cell Epitope ◽

T Cell Epitope

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Mining the capacity of human-associated microorganisms to trigger rheumatoid arthritis—A systematic immunoinformatics analysis of T cell epitopes

PLoS ONE ◽

10.1371/journal.pone.0253918 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0253918

Author(s):

Jelena Repac ◽

Marija Mandić ◽

Tanja Lunić ◽

Bojan Božić ◽

Biljana Božić Nedeljković

Keyword(s):

Rheumatoid Arthritis ◽

T Cell ◽

De Novo ◽

Molecular Mimicry ◽

Sequence Similarity ◽

Cell Epitope ◽

Homology Search ◽

T Cell Epitope ◽

T Cell Epitopes ◽

Painful Condition

Autoimmune diseases, often triggered by infection, affect ~5% of the worldwide population. Rheumatoid Arthritis (RA)–a painful condition characterized by the chronic inflammation of joints—comprises up to 20% of known autoimmune pathologies, with the tendency of increasing prevalence. Molecular mimicry is recognized as the leading mechanism underlying infection-mediated autoimmunity, which assumes sequence similarity between microbial and self-peptides driving the activation of autoreactive lymphocytes. T lymphocytes are leading immune cells in the RA-development. Therefore, deeper understanding of the capacity of microorganisms (both pathogens and commensals) to trigger autoreactive T cells is needed, calling for more systematic approaches. In the present study, we address this problem through a comprehensive immunoinformatics analysis of experimentally determined RA-related T cell epitopes against the proteomes of Bacteria, Fungi, and Viruses, to identify the scope of organisms providing homologous antigenic peptide determinants. By this, initial homology screening was complemented with de novo T cell epitope prediction and another round of homology search, to enable: i) the confirmation of homologous microbial peptides as T cell epitopes based on the predicted binding affinity to RA-related HLA polymorphisms; ii) sequence similarity inference for top de novo T cell epitope predictions to the RA-related autoantigens to reveal the robustness of RA-triggering capacity for identified (micro/myco)organisms. Our study reveals a much larger repertoire of candidate RA-triggering organisms, than previously recognized, providing insights into the underestimated role of Fungi in autoimmunity and the possibility of a more direct involvement of bacterial commensals in RA-pathology. Finally, our study pinpoints Endoplasmic reticulum chaperone BiP as the most potent (most likely mimicked) RA-related autoantigen, opening an avenue for identifying the most potent autoantigens in a variety of different autoimmune pathologies, with possible implications in the design of next-generation therapeutics aiming to induce self-tolerance by affecting highly reactive autoantigens.

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