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bioRxiv · 10.1101/2024.12.17.628918

Ready-to-load MHC-I Nanoparticles for High-throughput T cell Screening Studies

Phan, H. A. T.·Hwang, D.·Young, M. C.·Sun, S. M.·Monos, D. S.·Sgourakis, N. G.
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Abstract

MHC-I proteins present epitopic peptides to CD8+ T cells to elicit multifaceted adaptive immune responses. The affinity and avidity of interactions between peptide-MHC molecules and T-cell receptors (TCR) are fundamental parameters that contribute to the induction of activated or anergic T cell states. Here, we present a loadable system, VLP-Open HLA, featuring a virus-like particle (VLP) that can accommodate up to 60 loadable HLA (HLA - human leukocyte antigen) molecules. HLA nanoparticles, pre-loaded with a placeholder ligand, allow efficient peptide exchange upon incubation with target peptides. We show that fluorescently tagged VLP-Open HLA particles can be used to stain antigen-specific CD8+ T cells, providing a screening tool for novel TCRs. Finally, we demonstrate that our system can induce activation of T cells in an antigen-specific manner. Our platform can be adapted to encompass multiple HLA allotypes and co-stimulatory molecules as mosaic nanoparticles, to enable a range of applications in experimental immunology.

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Phan, H. A. T., Hwang, D., Young, M. C., Sun, S. M., Monos, D. S., Sgourakis, N. G.. 2024-12-20. Ready-to-load MHC-I Nanoparticles for High-throughput T cell Screening Studies. https://doi.org/10.1101/2024.12.17.628918

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