Ready-to-load MHC-I nanoparticles for high-throughput T cell screening studies.

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 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.