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0This research introduces APMAT-CD4, a high-throughput platform designed to identify and characterize antigen-specific CD4+ T cells at single-cell resolution. The authors developed a modular system using class II single-chain trimer libraries to overcome the technical challenges of profiling helper T cells across multiple dimensions, including TCR sequences, transcriptomes, and MHC restriction. The technology was validated by screening SARS-CoV-2 spike proteins in a longitudinal cohort, revealing how immunogenicity scores relate to antibody production and disease progression. Furthermore, the platform was applied to HPV-16 oncoproteins, identifying therapeutic T cell receptors with strong potential for cancer immunotherapy. By integrating whole-protein screening with multi-modal profiling, this approach offers a comprehensive framework for advancing vaccine design and precision medicine.
References:
Zhang R, Qi J, McKasson M, Choi J, Gutierrez V, Brennan C, Hong S, Chour W, Ng RH, Xie J, Yuan D, Webster A, Sidhu SK, Anderson A, Chen D, Edmark R, Murray KM, Li S, McDonald C, Rowen L, Wang S, Rasheed Y, Su Y, Wagner JR, Chen JM, Nawaly K, Fu J, Duven A, Forman SJ, Song M, Priceman SJ, Brown CE, Ribas A, Wong DJ, Paulson KG, Drescher CW, Puig-Saus C, Goldman JD, Trimble CL, Heath JR. Whole-protein screening and multi-modal profiling of antigen-specific CD4+ T cells at single-cell resolution. Nat Commun. 2026 May 12;17(1):3979. doi: 10.1038/s41467-026-72396-7. PMID: 42120368; PMCID: PMC13168688.
