Ready-to-load MHC-I nanoparticles for high-throughput T cell screening studies
- Hoang Anh T. Phan
- Soomin Eom
- Daniel Hwang
- Michael C. Young
- Shirley M. Sun
- Molly C. Erdman
- Yi Sun
- Leena Mallik
- Photis Rotsides
- Mark M. Painter
- E. John Wherry
- Dimitri S. Monos
- Nikolaos G. Sgourakis
2026-06-12
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 their cognate T cell receptors (TCRs) are fundamental parameters that contribute to the induction of activated or anergic T cell states. Here, we present a multivalent, loadable platform, VLP-Open HLA, featuring a virus-like particle (VLP) which can display up to 60 peptide/HLA [human leukocyte antigen (HLA)] molecules. VLP-Open HLA can be used to stain antigen-specific CD8 + T cells, providing a screening tool for orphan TCRs. When combined with costimulation, VLP-Open HLA acts as an artificial antigen-presenting platform to induce antigen-specific T cell activation and expansion, providing a facile alternative to autologous antigen-presenting cells. Our platform can be adapted to encompass multiple HLA allotypes and costimulatory molecules as mosaic nanoparticles, enabling a range of applications in experimental immunology.