Immunity system complexity: more on T cell controls (Introduction)

by David Turell , Monday, August 15, 2022, 22:21 (830 days ago) @ David Turell

New more exact studies:

"How do killer T cells recognize cells in the body that have been infected by viruses? Matter foreign to the body is presented on the surface of these cells as antigens that act as a kind of road sign. A network of accessory proteins -- the chaperones -- ensure that this sign retains its stability over time. Researchers have now reached a comprehensive understanding of this essential cellular quality control process.

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"Humans possess a repertoire of some 20 million T cell clones with varying specificity to counter the multitude of infectious agents that exist. But how do the killer T cells know where danger is coming from? How do they recognise that something is wrong inside a cell in which viruses are lurking? They can't just have a quick peek inside.

"At this point, antigen processing comes into play. The process can be compared to making a road sign. The molecular barcode is "processed" or assembled in the cell -- in the endoplasmic reticulum, to be exact. Special molecules are used in its making, the MHC class I molecules. They are loaded with information about the virus invader in a molecular machine, the peptide loading complex (PLC). This information consists of peptides, fragments of the protein foreign to the body. These fragments also contain epitopes, the molecular segments that elicit a specific immune response. During the loading process, an MHC I-peptide epitope complex thus forms, and this is the road sign that is then transported to the surface of the cell and presented in a readily accessible form to the killer T cells --

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"He explains the logic underlying this quality control process as follows: "The MHC I-peptide epitope complex, the road sign, needs to be exceptionally stable, and for quite a long time, because the adaptive immune response does not start instantly. It needs 3 to 5 days to get going." So, the sign must not collapse after one day; that would be disastrous, as the immune defence cells would then fail to detect cells infected by a virus. This would mean that they would not destroy these cells and the virus would be able to continue its spread unhindered. A similar problem would arise if a cell in the body had mutated into a tumour cell: the threat would remain undetected. It is imperative, therefore, that a quality control system is in place.

"As the study shows, the chaperones are central process components: they give the road sign the long-term stability it must have by making a strict selection. By rejecting the short-lived virus fragments in the mass of available material, they ensure that only MHC I molecules loaded with the best and most stable peptide epitopes in complex with MHC I are released from the peptide loading complex. The chaperones have different tasks in this selection process that is so important for the adaptive immune response, Tampé says: "Tapasin acts as a catalyst that accelerates the exchange of suboptimal peptide epitopes for optimal epitopes. Calreticulin and ERp57, in contrast, are deployed universally." This concerted approach ensures that only stable MHC I complexes with optimal peptide epitopes reach the cell surface and perform their role of guiding the killer T cells to the infected or mutated cell."

Comment: Thes tags will now permanently be available for the next attack. The library builds throughout a lifetime, all done by molecules under tight design controls.