TCR-pMHC recognition mediates target phagocytosis by T cells

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• T cells are traditionally considered non-phagocytic, with phagocytosis performed by professional phagocytes like macrophages.
• T cell function is primarily mediated through T cell receptor (TCR) recognition of antigens presented by peptide-MHC (pMHC) complexes at the immunological synapse.

Purpose of the Study:

• To investigate if T cell receptor (TCR) recognition of peptide-MHC (pMHC) complexes alone can induce phagocytosis in T cells.
• To explore the potential of engineering T cells for novel effector functions, such as phagocytosis.

Main Methods:

• Generated CD8+ Jurkat T cells expressing a specific human TCR (SVAR16) with affinity for a SARS-CoV-2 epitope (HLA*A2:01-YLQ).
• Utilized a micropipette system to control and image T cell interactions with pMHC-coated beads.
• Observed and quantified phagosome formation and bead internalization kinetics.

Main Results:

• Cognate pMHC recognition by engineered T cells was sufficient to induce rapid, antigen-specific phagocytosis.
• CD8+ Jurkat T cells formed phagosomes and internalized pMHC-coated beads within minutes.
• TCR-pMHC interactions, supported by CD8 co-receptors, converted T cells into antigen-specific phagocytes.

Conclusions:

• TCR-pMHC interactions can drive antigen-specific phagocytosis in T cells, demonstrating a novel effector function.
• TCR engineering holds potential for converting T cells into phagocytes, opening new avenues for T cell-based cancer immunotherapy.