TCR-pMHC recognition mediates target phagocytosis by T cells.

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.