TCR-pMHC recognition mediates target phagocytosis by T cells

Abstract

T cells are traditionally viewed as non-phagocytic lymphocytes that recognize antigens via the T cell receptor (TCR) and mediate cytotoxicity at the immunological synapse, while phagocytosis is performed by professional phagocytes such as macrophages and dendritic cells. Here we show that peptide–MHC (pMHC) recognition alone is sufficient to drive rapid, antigen-specific phagocytosis by Jurkat T cells. We generated CD8⁺ Jurkat cells expressing a class I–restricted human TCR (SVAR16) with intermediate-to-high 2-dimensional (2D) affinity for the SARS-CoV-2 epitope HLA∗A2:01–YLQ and used a micropipette system to control and image T cell interaction with pMHC coated beads. Upon contact with cognate YLQ-coated beads, SVAR16 transduced CD8⁺ Jurkat cells consistently formed phagosomes within minutes and completely internalized beads with consistent kinetics. These results demonstrate that appropriately tuned TCR–pMHC interactions, supported by CD8 co-receptors, can convert a canonical CD4⁺ T cell line into an antigen-specific phagocyte. This work reports a novel effector function of T cells and suggests that TCR-engineering could convert CD4⁺ T cells into phagocytes, potentially revealing a new approach to T cell-based cancer immunotherapy.