Proteome-Wide Zika Virus CD4 T Cell Epitope and HLA Restriction Determination

Campbell, Victoria; Nguyen, LeAnn P.; Snoey, Elise; McClurkan, Christopher L.; Laing, Kerry J.; Dong, Lichun; Sette, Alessandro; Arlehamn, Cecilia S. Lindestam; Altmann, Daniel M.; Boyton, Rosemary J.; Roby, Justin A; Gale, Michael; Stone, Mars; Busch, Michael P.; Norris, Phillip J.; Koelle, David M.

doi:10.4049/immunohorizons.2000068

Cited by 10 publications

(12 citation statements)

References 49 publications

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“…This strategy is therefore particularly effective when an educated guess or inference of HLA restriction is available. An alternative methodology is the use of single HLA transfected APCs [102,[130][131][132][133]. In these experiments, the peptide is tested in antigen presentation assays utilizing panels of cell lines expressing single HLA molecules that match an allele expressed in the donor from which the T cell response is generated.…”

Section: Hla Restriction Of Epitope Responsesmentioning

confidence: 99%

Epitope prediction and identification- adaptive T cell responses in humans

Sidney

Peters

Sette

2020

Seminars in Immunology

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Section: Hla Restriction Of Epitope Responsesmentioning

confidence: 99%

Epitope prediction and identification- adaptive T cell responses in humans

Sidney

Peters

Sette

2020

Seminars in Immunology

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“…Most of the vaccines against SARS-CoV-2 are in development, under trials or in emergency usage are targeting the humoral immune response for making neutralizing antibodies (Amanat and Krammer 2020 ; Le et al 2020 ). However, the concept of acquired, specific T cell immunity becomes crucial in context of vaccination to clear viral infections and enhance neutralizing antibody responses (Campbell et al 2020 ). Many studies have reported a higher frequency of Spike protein specific CD4 T cell responses and heightened CD8 T cell responses specific to other internal proteins of SARS-CoV-2 in convalescent individuals (Grifoni et al 2020 ; Sekine et al 2020 ; Dong et al 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the role of CD4 T cell epitope based viral vaccine cannot be overlooked given their ability to enhance activation of CD8 T cell, inducing protective CD8 T cell memory and prolonging their antiviral function (Phares et al 2012 ). Additionally, CD4 T cells also trigger antigen-specific B cells immunoglobulin class switching and affinity maturation (Campbell et al 2020 ).Yet, an exaggerated and distinctive pro-inflammatory response is also reported with reference to severity of COVID-19 disease (Johnson and Laloraya 2020 ). Nonetheless, balance in the pro-inflammatory and anti-inflammatory immune responses determines the outcome of any bacterial or viral infection.…”

Section: Introductionmentioning

confidence: 99%

Prediction and identification of T cell epitopes of COVID-19 with balanced cytokine response for the development of peptide based vaccines

Medha

Bhatt

Choudhary

et al. 2021

In Silico Pharmacol.

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Recent outbreak of 2019 novel Corona virus poses serious challenge for the global health system. In lieu of paucity of experimental data, tools and the very basic understanding of host immune responses against SARS-CoV-2, well thought effective measures are needed to control COVID-19 pandemic. We have identified specific overlapping antigenic peptide epitopes (OAPE) within the 4 structural proteins of SARS-CoV-2 predictive of triggering robust CD4 and CD8 T cell responses in host using bio-informatics tools (NetMHC4.0, IEDB, and Vaxijen2.0). We speculate an early release of pro-inflammatory cytokines for protection and later release of anti-inflammatory cytokines for prevention of immunopathology in designing a vaccine for Covid-19. Therefore, the selected immunogenic OAPE were subjected to in silico tools (IL-6-Pred, IFNepitope and PIP-EL) for analyzing their pro-inflammatory response. The OAPEs found to be pro-inflammatory in nature were further subjected to prediction servers (IL-4-Pred, IL-10-Pred, Pre-AIP) to characterize them as inducers of anti-inflammatory response as well. We finally filtered out 12 OAPE which had affinity for both CD4 and CD8 T cells as well as were inducers of pro-inflammatory and anti-inflammatory cytokines. On confirmation of OAPE binding affinity for respective T cell specific MHC allele using docking studies (pepATTRACT, Hex8.0 and Discovery studio) they were found to be have more immunogenic potential than the 3 negative control peptides (NCPs) included in the study. Additionally, we constructed CTxB-adjuvanated multi-epitopic vaccine inclusive of the 12 OAPEs which was non-toxic, non-allergenic and capable of inducing both pro-inflammatory and anti-inflammatory cytokines. A successful in silico cloning and docking of modeled subunit vaccine construct with toll like receptor-2 (TLR-2) confirmed the high efficacy of our multi-epitopic vaccine which can through a balanced interplay of cytokines help in creating a steady-state immune equilibrium. In silico immune simulation studies with the vaccine using C-ImmSim server also showed higher percentage of T cells along with production of pro-inflammatory as well as some anti-inflammatory cytokines. Experimental validation of this prediction based study on Peripheral Blood Mononuclear Cells (PBMCs) of un-infected individuals, patients and recovered individuals will facilitate production of high priority effective SARS -CoV-2 vaccine candidate. Supplementary Information The online version contains supplementary material available at 10.1007/s40203-021-00098-7.

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“…We defined CD4 TCL HLA restriction as published (40). First, serial dilutions of peptide (1, 0.1, or 0.01 μg/ml) were tested in triplicate using autologous EBV-LCL as APC without or with mAbs that block HLA DR, DP, or DQ (100).…”

Section: Methodsmentioning

confidence: 99%

“…First, serial dilutions of peptide (1, 0.1, or 0.01 μg/ml) were tested in triplicate using autologous EBV-LCL as APC without or with mAbs that block HLA DR, DP, or DQ (100). To determine allele-level restriction, engineered APC expressing single HLA class II heterodimers were selected (40) to match the study subject. Negative controls were cells parental to the single antigen line (SAL).…”

Section: Methodsmentioning

confidence: 99%

T cell response to intact SARS-CoV-2 includes coronavirus cross-reactive and variant-specific components

Jing

Krist

et al. 2022

Preprint

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SARS-CoV-2 provokes a brisk T cell response. Peptide-based studies exclude antigen processing and presentation biology and may influence T cell detection studies. To focus on responses to whole virus and complex antigens, we used intact SARS-CoV-2 and full-length proteins with DC to activate CD8 and CD4 T cells from convalescent persons. T cell receptor (TCR) sequencing showed partial repertoire preservation after expansion. Resultant CD8 T cells recognize SARS-CoV-2-infected respiratory cells, and CD4 T cells detect inactivated whole viral antigen. Specificity scans with proteome-covering protein/peptide arrays show that CD8 T cells are oligospecific per subject and that CD4 T cell breadth is higher. Some CD4 T cell lines enriched using SARS-CoV-2 cross-recognize whole seasonal coronavirus (sCoV) antigens, with protein, peptide, and HLA restriction validation. Conversely, recognition of some epitopes is eliminated for SARS-CoV-2 variants, including spike (S) epitopes in the alpha, beta, gamma, and delta variant lineages.

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Proteome-Wide Zika Virus CD4 T Cell Epitope and HLA Restriction Determination

Cited by 10 publications

References 49 publications

Epitope prediction and identification- adaptive T cell responses in humans

Epitope prediction and identification- adaptive T cell responses in humans

Prediction and identification of T cell epitopes of COVID-19 with balanced cytokine response for the development of peptide based vaccines

T cell response to intact SARS-CoV-2 includes coronavirus cross-reactive and variant-specific components

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