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J. Göhring, F. Kellner, L. Schrangl, R. Platzer, E. Klotzsch, H. Stockinger, J. Huppa, G. Schütz:
"Temporal Analysis of T-Cell Receptor-Imposed Forces via Quantitative Single Molecule FRET Measurements";
Nature Communications, 12 (2021), 250201 - 250214.

Aremarkable feature of the vertebrates´ immune system is
its inherent ability to distinguish harmful from harmless
based on the primary antigen structure. T-cells embody
this trait of adaptive immunity through their unique detection of
antigens, which are displayed as peptide fragments in the context
of the products of the major histocompatibility complex (MHC)
on the surface of antigen-presenting cells (APCs). The formation
of a productive immunological synapse, the area of contact
between a T-cell and an APC1, is driven by T-cell antigen
receptors (TCRs) on the T-cell binding to peptide/MHC com-
plexes (pMHC) on the APC. Importantly, T-cells specifically
detect the presence of even a single antigenic pMHC molecule
among millions of structurally similar yet non-stimulatory
pMHCs2. This is even though nominal pMHC-TCR interac-
tions are of a rather moderate affinity, at least when measured
in vitro. Despite considerable interest, the molecular, biophysical,
and cellular mechanisms underlying this phenomenal sensitivity
and specificity are not well understood.

http://dx.doi.org/10.1038/s41467-021-22775-z