Tetramer-Guided Epitope Mapping: A Rapid Approach to Identify HLA-Restricted T-Cell Epitopes from Composite Allergens

Archila, Luis L. Diego; Kwok, William W.

doi:10.1007/978-1-4939-6925-8_16

Cited by 11 publications

(9 citation statements)

References 16 publications

(16 reference statements)

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“…These tetramer complexes are now considered the gold standard for identifying allergen-specific T cells. Construction of these tetramers, however, requires prior knowledge of the specific peptide-MHC components involved, limiting its routine use (41)(42)(43). Further improvements to this technology include a next-generation peptide-MHC dodecamer, which is able to detect 2-to 5-fold more antigen-specific T cells than tetramers (44).…”

Section: T Cell Mechanisms Underlying Tolerancementioning

confidence: 99%

Newly identified T cell subsets in mechanistic studies of food immunotherapy

Sampath¹,

Nadeau²

2019

Journal of Clinical Investigation

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Section: T Cell Mechanisms Underlying Tolerancementioning

confidence: 99%

Newly identified T cell subsets in mechanistic studies of food immunotherapy

Sampath¹,

Nadeau²

2019

Journal of Clinical Investigation

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“…This mass spectrometry data enabled us to train neural network-based binding predictors that outperform the leading affinity-based predictors for both HLA-I (26) and HLA-II (27). Furthermore, we demonstrated in (27) that this improved binding prediction leads to improved immunogenicity prediction by validating on a data set of tetramer responses to a diverse collection of pathogens and allergens (28,29). Although RECON was originally developed to prioritize neoantigens for immunotherapy applications, it is agnostic to the source of peptide sequences evaluated and can be easily applied to peptides derived from pathogens as well.…”

Section: Introductionmentioning

confidence: 95%

Sequence-based prediction of vaccine targets for inducing T cell responses to SARS-CoV-2 utilizing the bioinformatics predictor RECON

Poran¹,

Harjanto²,

Malloy³

et al. 2020

Preprint

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BackgroundThe ongoing COVID-19 pandemic has created an urgency to identify novel vaccine targets for protective immunity against SARS-CoV-2. Consistent with observations for SARS-CoV, a closely related coronavirus responsible for the 2003 SARS outbreak, early reports identify a protective role for both humoral and cell-mediated immunity for SARS CoV-2.MethodsIn this study, we leveraged HLA-I and HLA-II T cell epitope prediction tools from RECON® (Real-time Epitope Computation for ONcology), our bioinformatic pipeline that was developed using proteomic profiling of individual HLA-I and HLA-II alleles to predict rules for peptide binding to a diverse set of such alleles. We applied these binding predictors to viral genomes from the Coronaviridae family, and specifically to identify SARS-CoV-2 T cell epitopes.ResultsTo test the suitability of these tools to identify viral T cell epitopes, we first validated HLA-I and HLA-II predictions on Coronaviridae family epitopes deposited in the Virus Pathogen Database and Analysis Resource (ViPR) database. We then use our HLA-I and HLA-II predictors to identify 11,776 HLA-I and 7,991 HLA-II candidate binding peptides across all 12 open reading frames (ORFs) of SARS-CoV-2. This extensive list of identified candidate peptides is driven by the length of the ORFs and the significant number of HLA-I and HLA-II alleles that we are able to predict (74 and 83, respectively), providing over 99% coverage for the US, European and Asian populations, for both HLA-I and HLA-II. From our SARS-CoV-2 predicted peptide-HLA-I allele pairs, 368 pairs identically matched previously reported pairs in the ViPR database, originating from other forms of coronaviruses. 320 of these pairs (89.1%) had a positive MHC-binding assay result. This analysis reinforces the validity our predictions.ConclusionsUsing this bioinformatic platform, we identify multiple putative epitopes for CD4+ and CD8+ T cells whose HLA binding properties cover nearly the entire population and thus may be effective when included in prophylactic vaccines against SARS-CoV-2 to induce broad cellular immunity.

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“…We therefore used a more reductionist approach, using MHC II tetramer-guided epitope mapping (TGEM) 11 to identify a single peptide epitope from the bacterial antigen OmpC recognized by HLA-DRB1∗15:01-restricted T cells. We then were able to identify, quantify, characterize, and isolate individual HLA-DRB1∗15:01-restricted T cells specific for this OmpC peptide from the peripheral blood.…”

mentioning

confidence: 99%

Escherichia coli–Specific CD4+ T Cells Have Public T-Cell Receptors and Low Interleukin 10 Production in Crohn’s Disease

Uchida

Boden²,

James

et al. 2020

Cellular and Molecular Gastroenterology and Hepatology

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Background & Aims Crohn’s disease (CD) likely represents decreased immune tolerance to intestinal bacterial antigens. Most CD patients have high titers of antibodies to intestinal commensal proteins, including the outer membrane porin C (OmpC) of Escherichia coli . Methods By using major histocompatibility complex II tetramers, we identified an HLA-DRB1∗15:01-restricted peptide epitope of OmpC recognized by CD4+ T cells in peripheral blood mononuclear cells from HLA-DRB1∗15:01+ healthy control (HC) and CD patients. Results The precursor frequency of these cells in CD correlated with anti-OmpC IgA titers, but did not differ from that of HCs. In both cohorts, they showed a CD161+, integrin α4β7+ phenotype ex vivo by flow cytometry, distinct from the C-X-C Motif Chemokine Receptor 3 phenotype of autologous influenza hemagglutinin (Flu) peptide-specific T cells. The T-cell receptor α and β chains of in vitro–expanded OmpC-specific T-cell clones often contained public amino acid sequences that were identical in cells from different patients. Expanded T-cell clones from CD subjects produced significantly less interleukin (IL)10 ( P < .0001) than those from HCs, and a trend toward decreased production of the T helper 2 cell–associated IL4, IL5, and IL13 by CD clones also was seen. Conclusions Both HCs and CD patients have detectable OmpC-specific T cells in circulation, with similar immunophenotypes and often identical T-cell–receptor sequences. However, expanded clones from patients with CD produce less of the immunoregulatory cytokine IL10, showing a selective defect in the regulatory function of intestinal microbial antigen-specific T cells in patients with CD.

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Tetramer-Guided Epitope Mapping: A Rapid Approach to Identify HLA-Restricted T-Cell Epitopes from Composite Allergens

Cited by 11 publications

References 16 publications

Newly identified T cell subsets in mechanistic studies of food immunotherapy

Newly identified T cell subsets in mechanistic studies of food immunotherapy

Sequence-based prediction of vaccine targets for inducing T cell responses to SARS-CoV-2 utilizing the bioinformatics predictor RECON

Escherichia coli–Specific CD4+ T Cells Have Public T-Cell Receptors and Low Interleukin 10 Production in Crohn’s Disease

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