One-step shotgun approach for antigenic specific pMHCs capture stimulated CD8+ T cell activation and proliferation

Abstract

Antigenic peptides play a central role in immune surveillance in cancer, infectious disease, autoimmunity, and allergy. The identification and isolation of antigenic peptides for T cell immune response are crucial for successful personalized adoptive immune cell therapy. The mainly methods includes gene sequencing and bioinformatic analysis. The antigenic peptides which identified by analysis and artificially synthesized still need antigen presenting cell (APC) to deliver to T cells. However, high costs and lengthy process times have limited its application in clinical practice. In order to overcome it, this study attempted to directly capture antigenic peptide-major histocompatibility complex (MHC) class I (pMHCs) from cell lysates using streptavidin Dynabeads and biotin-labeled antibodies, then the pMHCs was co-cultured with tumor infiltrating lymphocytes (TILs) of the same tissue origin. The results indicated that the captured pMHCs were able to enrich the tumor antigen-specific CD8⁺ T cells, and also effectively induce proliferation and cytotoxic responses of CD8⁺ T cells. This study provided a novel approach for obtaining tumor antigenic pMHCs, which could enrich antigen-specific CD8⁺ T cells, and could also function as artificial APCs (aAPCs) to stimulate proliferation and activation of T cells. Notably, these pMHCs can stimulate the proliferation of stem-like memory T cells. In conclusion, this study describes a time-saving and low-cost method to isolate tumour antigen peptide MHC complexs, helping tumor antigen-specific T cell enrichment, activation, and proliferation.