Defining T cell receptor repertoires using nanovial-based binding and functional screening.

Autor:	Koo D; Department of Bioengineering, University of California, Los Angeles, CA 90095., Mao Z; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095., Dimatteo R; Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095., Noguchi M; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095., Tsubamoto N; Department of Bioengineering, University of California, Los Angeles, CA 90095., McLaughlin J; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095., Tran W; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095., Lee S; Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095., Cheng D; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095., de Rutte J; Department of Bioengineering, University of California, Los Angeles, CA 90095.; Partillion Bioscience, Pasadena, CA 91107., Burton Sojo G; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095., Witte ON; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095.; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095.; Molecular Biology Institute, University of California, Los Angeles, CA 90095.; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095.; Parker Institute for Cancer Immunotherapy, David Geffen School of Medicine, University of California, Los Angeles, CA 90095., Di Carlo D; Department of Bioengineering, University of California, Los Angeles, CA 90095.; Partillion Bioscience, Pasadena, CA 91107.; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095.; Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, CA 90095.; California NanoSystems Institute, Los Angeles, CA 90095.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Apr 02; Vol. 121 (14), pp. e2320442121. Date of Electronic Publication: 2024 Mar 27.
DOI:	10.1073/pnas.2320442121
Abstrakt:	The ability to selectively bind to antigenic peptides and secrete effector molecules can define rare and low-affinity populations of cells with therapeutic potential in emerging T cell receptor (TCR) immunotherapies. We leverage cavity-containing hydrogel microparticles, called nanovials, each coated with peptide-major histocompatibility complex (pMHC) monomers to isolate antigen-reactive T cells. T cells are captured and activated by pMHCs inducing the secretion of effector molecules including IFN-γ and granzyme B that are accumulated on nanovials, allowing sorting based on both binding and function. The TCRs of sorted cells on nanovials are sequenced, recovering paired αβ-chains using microfluidic emulsion-based single-cell sequencing. By labeling nanovials having different pMHCs with unique oligonucleotide-barcodes and secretions with oligo-barcoded detection antibodies, we could accurately link TCR sequences to specific targets and rank each TCR based on the corresponding cell's secretion level. Using the technique, we identified an expanded repertoire of functional TCRs targeting viral antigens with high specificity and found rare TCRs with activity against cancer-specific splicing-enhanced epitopes. Competing Interests: Competing interests statement:J.d.R. is an employee of Partillion Bioscience which is commercializing nanovial technology. J.d.R., D.D.C. and the University of California have financial interests in Partillion Bioscience. O.N.W. currently has consulting, equity, and/or board relationships with Trethera Corporation, Kronos Biosciences, Sofie Biosciences, Breakthrough Properties, Vida Ventures, Nammi Therapeutics, Two River, Iconovir, Appia BioSciences, Neogene Therapeutics, 76Bio, and Allogene Therapeutics. Some of authors are inventors on patent application owned by the University of California.
Databáze:	MEDLINE
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