Biomolecular Recognition: The Current Challenge - Dynamic Force Spectroscopy and Biomolecular Recognition - page 8

T

TCR

p p

CD8

MHC

APC

FIGURE 1.3 (See color insert.) T cell activation. A CD4 or CD8 (shown here) T lympho-
cyte (T) interacting with an antigen-presenting cell (APC) is endowed with several tens of
thousands of identical T cell receptors (TCR) specific for a unique combination of a MHC
molecule and an oligopeptide resulting from the degradation of a particular protein. There
may be only a few tens, or less, of specific ligands of a TCR on an APC.

activation since a too-short interaction might result in cell paralysis rather than
activation of effector functions [126]. Thus, quantifying these interactions between
membrane-bound receptors and ligands is a current challenge of prominent impor-
tance [89] [90].
While the aforementioned two recognition mechanisms have been a focus of
intense investigation during the last three or four decades, it is well recognized
that the immune function also requires a set of so-called innate recognition mech-
anisms that are able to detect foreign microorganisms or damaged cells. Thus, a
variety of receptors such as scavenger receptors [82] or toll-like receptors [91] can
detect remarkable structures such as double-stranded ribonucleic acids, which are not
expressed by eukaryotic cells or denatured proteins and altered lipids that appear in
damaged cells. The exquisite specificity of antibodies and TCRs may be responsible
for the necessity of an additional recognition mechanism: Since a given lymphocyte
bears receptors of a single specificity (this is a basic tenet of the so-called clonal the-
ory), due to the high amount of receptor specificities, the probability that a foreign
particle entering a multicellular organism be recognized by a lymphocyte it had just
encountered is very low. Since immune defenses would be uneffective if an exces-
sive amount of time was required to initiate an immune response, there is a need
for rapid ways of detecting the presence of foreign material with limited specificity.
Understanding the involved recognition mechanisms is a challenge of high current
interest.

1.2.5 S IGNAL G ENERATION

A general consequence of biorecognition events is the selective binding of specific
molecules by cell membrane receptors and subsequent generation of intracellular
signals that drive cell function. It has long been considered that this phenomenon
was fully accounted for by the specificity of intermolecular recognition events. Also,
signal generation was usually ascribed to two prominent mechanisms: (1) in many