PNAS: How the immune system identifies potential intruders.

September 18, 2020 /--- In a recent study, Dr. Wonmuk Hwang et al. revealed how various components of the body's immune system detect the intrinsic mechanisms of invasive or damaged cells, which may help develop new viruses and cancer treatments.
results were published in the journal PNAS.
(Photo: www.pixabay.com) When the virus enters the body, the immune system starts to function to find and destroy intruders.
T cells are an integral part of the immune system, looking for viruses hidden in host cells as the ultimate defense line against antigens or foreign property.
T cells detect the surface of other cells, examine the material that flows out of the cell, and are presented by the main tissue compatible complex (MHC) molecules on the cell surface.
problem is that only a small portion of the thousands of MHC molecules can present peptide segments from invading cells, " says Hwang.
means that T cells need to work like needles in a haystack.
recently found that T-cells mechanically improve their detection ability: when T-cells detect the surface of other cells, they produce natural contact.
if the cell is infected by an antigen, the force applied will cause a "capture bond" between the T-cell acceptor (TCR) and the MHC molecule to form, thus enhancing contact.
key does not appear between TCR and MCH molecules that do not carry specific antigens.
since it is almost impossible to see this interaction in atomic detail through experiments, Hwang has developed a computer simulation tool that can truly demonstrate and analyze the interaction between TCR and MHC molecules when exerting force.
only simulation can see and analyze molecular motion under load," said Hwang, a research analyst.
structure of proteins as determined by experiments is a static snapshot, but when molecules move, motion is largely invisible.
" Hwang found how the motion between the parts of TCR controls their interactions with MHC molecules.
when applying force, motion is inhibited only when the MHC molecule has a matching antigen, thus stabilizing the entire complex.
other cases will reject interlocking with TCR, and the constant movement between the two will eventually cause them to disconnect.
like a lock and key system, where locks and keys change shape and molecules can only be interlocked if they are perfectly matched and at a sufficient level of force.
further research is needed to understand how this principle applies to different T-cell subjects," said Hwang, a researcher at the University of New China.
.com Source: Discoveries made in how immune system detects hidden intruders Original source: Wonmuk Hwang et al, The alpha beta TCR mechanosens exploitsors dynamic ectodomain allostery to optimize its ligand recognition site, Proceedings of the National Academy of Sciences (2020). DOI: 10.1073/pnas.2005899117.