A ‘protein bomb’ used by the immune system to kill infected and cancerous cells

Authors: Michael Dustin (University of Oxford)
Co-authored by industrial partner: No

Type: Diamond Annual Review Highlight

State: Published (Approved)
Published: July 2021
Diamond Proposal Number(s): 23000

Abstract: Cytotoxic T cells (CTLs) kill infected and cancerous cells by secreting cytotoxic proteins. An international team of researchers investigated how these cytotoxic proteins avoid dilution in the vast extracellular space and enter target cells that need to be killed. The question they were seeking to answer was whether these proteins organise into particles. Diamond Light Source's 3D X-ray tomography and super resolution fluoresence microscopy for the life sciences beamline (B24) uses soft (low-energy) X-rays to generate 3D maps of organic material in cells and small particles released from cells. For this research, B24 provided correlative information about ‘protein bombs’ released by cytotoxic T cells and within the cells. Soft X-rays were better than electrons in this case as they allow imaging of entire T cells, although the resolution is lower. The results allowed the team to confirm that the ‘protein bombs’ had a ‘core-shell’ structure and identify potential storage sites for the ‘protein bombs’ in the T cells. Whereas most biological drugs are single protein molecules, ‘protein bombs’ are ‘supramolecular’, a loose assembly of hundreds or thousands of proteins that deliver the active components to targets in the body. These ‘protein bombs’ have the potential to be used in immunotherapy applications, which help the body’s immune system to fight cancer and other diseases. One of the next steps for the research team is to try to make synthetic ‘protein bombs’. B24 will be helpful in characterising these ‘supramolecular’ drugs.

Journal Keywords: Immunology; Immunotherapy; Apoptosis; Secretion; Synapse; 3D imaging; Cryo Soft X-ray Tomography (CSXT); Correlative Light and X-ray Tomography (CLXT)

Diamond Keywords: Viruses; Immunotherapy

Subject Areas: Biology and Bio-materials

Instruments: B24-Cryo Soft X-ray Tomography

Added On: 12/11/2021 11:03

Discipline Tags:

Pathogens Non-Communicable Diseases Infectious Diseases Health & Wellbeing Cancer Structural biology Life Sciences & Biotech

Technical Tags:

Imaging Tomography