B cells modulate mouse allergen-specific T cells in nonallergic laboratory animal-care workers

Yu, Esther Dawen; Westernberg, Luise; Grifoni, Alba; Sutherland, Aaron; Wang, Eric; Peters, Bjoern; Antunes, Ricardo da Silva; Sette, Alessandro

doi:10.1172/jci.insight.145199

Cited by 3 publications

(4 citation statements)

References 29 publications

(29 reference statements)

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“…Representative data for γδ T cell reactivity using the AIM assay and stimulation with a MO allergen extract, which we have previously extensively characterized in the study of conventional mouse-specific αβ T cells responses, 40 , 41 , 42 , 43 is shown in Figure 1 A. MO-specific γδ T cell responses were readily observed in all donors (33/33) with a wide range of reactivity (median: 16.91%, range: 2.07%–50.42%) ( Figure 1 B). Levels of background activation seen without stimulation (Neg) are measurable and also differ between individuals, albeit approximately (approx.)…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies established that allergen-specific αβ T cell responses are also readily detected in non-allergic subjects, albeit with different frequencies and/or functionality when compared with allergic subjects. 40 , 42 , 43 , 46 , 47 Accordingly, we next examined whether allergen-specific γδ T cell responses could also be detected in non-allergic donors. To this end, we utilized PBMCs from a cohort of 39 healthy donors who had no clinical symptoms for MO, CR, HDM, or TG allergies and negative laboratory evidence of sensitization as defined by plasma-allergen-specific IgE levels of <0.10 kUA/L.…”

Section: Resultsmentioning

confidence: 99%

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Ex vivo assays show human gamma-delta T cells specific for common allergens are Th1-polarized in allergic donors

Wang

Garrigan

et al. 2022

Cell Reports Methods

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Ex vivo assays show human gamma-delta T cells specific for common allergens are Th1-polarized in allergic donors

Wang

Garrigan

et al. 2022

Cell Reports Methods

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“…Some of the salient and original applications of MPs include the characterization of T cell responses to antigens identified by immunoproteomic approaches (Oseroff et al., 2017; Schulten et al., 2013) and epitopes differentially recognized in different clinical manifestations (asthma versus rhinitis) (Dillon et al., 2015) or different levels of sensitization (Schulten et al., 2019) and the detection of T cell responses in non‐allergic subjects. Interestingly, by probing these reagents, allergic and non‐allergic subjects were both found to mount T cell responses but were associated with different phenotypes (da Silva Antunes, Pham, et al., 2018; Grifoni, da Silva Antunes, et al., 2019; Hinz et al., 2016; Schulten, Westernberg, et al., 2018; Yu, Westernberg, et al., 2021). Moreover, specific mouse allergen–derived epitopes were identified by coupling mass spectrometry and bioinformatic approaches (da Silva Antunes, Pham, et al., 2018).…”

Section: Introductionmentioning

confidence: 99%

“…Dust mite peptide pools were used to define the transcriptional profiles associated with allergic asthma (Seumois et al., 2020), and timothy grass–specific and cockroach‐specific MPs were used to characterize T cell reactivity in the context of allergen‐specific immunotherapy (Rudman Spergel et al., 2021; Schulten et al., 2014; Schulten et al., 2016; Schulten, Tripple, et al., 2018). Lastly, timothy grass and mouse allergen MPs were used to study the modulation of T cell responses associated with allergen exposure in non‐allergic subjects (Hinz et al., 2016; Yu, Westernberg, et al., 2021) and, most recently, to reveal recognition of allergen‐specific responses by gamma delta T cells (Yu, Wang, Garrigan, Sutherland, et al., 2022).…”

Section: Introductionmentioning

confidence: 99%

The MegaPool Approach to Characterize Adaptive CD4+ and CD8+ T Cell Responses

da Silva Antunes,

Weiskopf,

Sidney

et al. 2023

Current Protocols

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Epitopes recognized by T cells are a collection of short peptide fragments derived from specific antigens or proteins. Immunological research to study T cell responses is hindered by the extreme degree of heterogeneity of epitope targets, which are usually derived from multiple antigens; within a given antigen, hundreds of different T cell epitopes can be recognized, differing from one individual to the next because T cell epitope recognition is restricted by the epitopes’ ability to bind to MHC molecules, which are extremely polymorphic in different individuals. Testing large pools encompassing hundreds of peptides is technically challenging because of logistical considerations regarding solvent‐induced toxicity. To address this issue, we developed the MegaPool (MP) approach based on sequential lyophilization of large numbers of peptides that can be used in a variety of assays to measure T cell responses, including ELISPOT, intracellular cytokine staining, and activation‐induced marker assays, and that has been validated in the study of infectious diseases, allergies, and autoimmunity. Here, we describe the procedures for generating and testing MPs, starting with peptide synthesis and lyophilization, as well as a step‐by‐step guide and recommendations for their handling and experimental usage. Overall, the MP approach is a powerful strategy for studying T cell responses and understanding the immune system's role in health and disease. © 2023 Wiley Periodicals LLC.Basic Protocol 1: Generation of peptide pools (“MegaPools”)Basic Protocol 2: MegaPool testing and quantitation of antigen‐specific T cell responses

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Advances in allergen‐specific immune cell measurements for improved detection of allergic sensitization and immunotherapy responses

Zelm

McKenzie

Varese

et al. 2021

Allergy

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Over the past two decades, precision medicine has advanced diagnostics and treatment of allergic diseases. Component-resolved analysis of allergen sensitization facilitates stratification of patients. Furthermore, new formulations of allergen immunotherapy (AIT) products can more effectively deliver the relevant components.Molecular insights from the identification of allergen component sensitization and clinical outcomes of treatment with new AIT formulations can now be utilized for a deeper understanding of the nature of the pathogenic immune response in allergy and how this can be corrected by AIT. Fundamental in these processes are the allergenspecific B and T cells. Within the large B-and T-cell compartments, only those that specifically recognize the allergen with their immunoglobulin (Ig) or T-cell receptor (TCR), respectively, are of clinical relevance. With peripheral blood allergen-specific B-and T-cell frequencies below 1%, bulk cell analysis is typically insufficiently sensitive. We here review the latest technologies to detect allergen-specific B and T cells, as well as new developments in utilizing these tools for diagnostics and therapy monitoring to advance precision medicine for allergic diseases.

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B cells modulate mouse allergen-specific T cells in nonallergic laboratory animal-care workers

Cited by 3 publications

References 29 publications

Ex vivo assays show human gamma-delta T cells specific for common allergens are Th1-polarized in allergic donors

Ex vivo assays show human gamma-delta T cells specific for common allergens are Th1-polarized in allergic donors

The MegaPool Approach to Characterize Adaptive CD4+ and CD8+ T Cell Responses

Advances in allergen‐specific immune cell measurements for improved detection of allergic sensitization and immunotherapy responses

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