De novo identification of CD4 + T cell epitopes.

Autor: Zdinak PM; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Systems Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Program in Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Trivedi N; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Systems Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Grebinoski S; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Program in Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Torrey J; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Systems Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Martinez EZ; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Systems Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Microbiology and Immunology Diversity Scholars Program, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Martinez S; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Systems Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Hicks L; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Systems Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Ranjan R; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Systems Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Makani VKK; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Systems Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Roland MM; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Systems Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Kublo L; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Systems Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Arshad S; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Systems Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Anderson MS; Diabetes Center, University of California San Francisco, San Francisco, CA, USA., Vignali DAA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA., Joglekar AV; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. joglekar@pitt.edu.; Center for Systems Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. joglekar@pitt.edu.; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. joglekar@pitt.edu.
Jazyk: angličtina
Zdroj: Nature methods [Nat Methods] 2024 May; Vol. 21 (5), pp. 846-856. Date of Electronic Publication: 2024 Apr 24.
DOI: 10.1038/s41592-024-02255-0
Abstrakt: CD4 + T cells recognize peptide antigens presented on class II major histocompatibility complex (MHC-II) molecules to carry out their function. The remarkable diversity of T cell receptor sequences and lack of antigen discovery approaches for MHC-II make profiling the specificities of CD4 + T cells challenging. We have expanded our platform of signaling and antigen-presenting bifunctional receptors to encode MHC-II molecules presenting covalently linked peptides (SABR-IIs) for CD4 + T cell antigen discovery. SABR-IIs can present epitopes to CD4 + T cells and induce signaling upon their recognition, allowing a readable output. Furthermore, the SABR-II design is modular in signaling and deployment to T cells and B cells. Here, we demonstrate that SABR-IIs libraries presenting endogenous and non-contiguous epitopes can be used for antigen discovery in the context of type 1 diabetes. SABR-II libraries provide a rapid, flexible, scalable and versatile approach for de novo identification of CD4 + T cell ligands from single-cell RNA sequencing data using experimental and computational approaches.
(© 2024. The Author(s).)
Databáze: MEDLINE
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