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New weapon identified in arsenal against disease

General Research

Researchers in the Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences (NDORMS) reveal supramolecular attack particles are autonomous killing entities released from cytotoxic T lymphocytes

Cryo-soft-x-ray tomography projection of a CD8+ T cell interacting with a carbon coated EM grid containing ICAM-1 and anti-CD3e (left). SMAPs (middle) can be observed within the multicore granules inside the cell. dSTORM images of an individual SMAP positive for perforin (green), WGA (orange) and granzyme B (magenta) released by CD8+ T cells (right)

Scientists at the Kennedy Institute of Rheumatology in the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS) have discovered a new way for T cells to attack cells infected by viruses or deranged by cancer.

Published online by the journal Science on Thursday 7 May 2020, the new research from the Dustin Group describes the structure and composition of supramolecular attack particles (SMAPs) and their role in killing targeted cells.

Cytotoxic T lymphocytes (CTLs) are essential components in the immune response against viruses and cancer. CTLs are known to recognise infected or damaged cells and release soluble protein molecules, which create perforations in the membrane of the targeted cell. These holes allow toxic enzymes to enter and initiate a self-destruct program, killing the targeted cell (cytotoxicity).

The new study reveals a complementary mechanism of cytotoxicity in the CTLs. The team identified SMAPs, ~120 nm diameter protein particles released by CTLs to kill other cells, for example, if virally infected or cancerous. SMAPs have a core of cytotoxic proteins surrounded by a glycoprotein shell.

Read more on the NDORMS website

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