Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 116

The immunological synapse is constituted by molecular complexes between
plasmalemmal and cytoplasmic substances on both sides, i.e., in the regions of
T and antigen-presenting cells. Between-cell communication is achieved first via
T-cell receptor that mediates recognition of complexes between foreign peptides and
major histocompatibility complex exhibited by antigen-presenting cells that primes
the transformation from quiescent to active T cells. Afterward, the microtubule-
organizing center polarizes to a position beneath the immunological synapse for
efficient protein secretion and a burst of actin polymerization happens at the contact
site with subsequent activation of integrins for cell adhesion [ 221 ].
The immunological synapse is a cellular junction composed of a central cluster
of T-cell receptors and a peripheral coat that contains α L β 2 -integrins. In addition,

T-cell receptors recruit their effectors, such as kinases, adaptors, and guanine
nucleotide-exchange factors. Cytokines and cytolytic molecules are released into
the immunological synapse between T lymphocytes and antigen-presenting cells
that occurs within minutes after activation of T-cell receptors (Table 3.20 ).

3.10.3 T-Lymphocyte Maintenance

Interleukin-7 promotes T-cell survival, as it elevates expression of the anti-apoptotic
molecule B-cell leukemia-lymphoma molecule (BCL2). Low-level activation of the
TCR signaling participates in the maintenance of T-cell homeostasis for both pro-
tective immunity and limitation of autoimmunity. 109 IL7 (IL7R) and T-cell (TCR)
receptor signaling are coordinated via cell division cycle CDC42 GTPase [ 222 ].
In the absence of CDC42, expression of growth factor-independent transcription
repressor GFI1 augments, that of IL7R decays, and aberrant activity of ERK1 and

ERK2 kinases enhances TCR-mediated T-cell proliferation. Regulation mediated by
CDC42 of T-cell activity relies on CDC42 effector P21-activated kinase PAK1. 110
Therefore, T-cell homeostasis is maintained through a synergystic regulation of
IL7 cytokine responsiveness and survival under the control of GFI1 and IL7R on the
one hand and strength of ERK-mediated TCR signaling regulated by the CDC42-
PAK1 axis on the other [ 222 ].

α

109 Interactions between MHC molecules and TCR initiate rearrangement of the actin cytoskeleton,
formation of immunological synapses, and activation of signaling effectors (ZAP70, LAT, MAPK,
etc.). Three CDC42 effectors, PAK1, WASP, and Par6, are involved in immunological synapse
formation and/or T-cell activation.
110 Once bound to CDC42, stimulated P21-activated kinase activates PI3K, JNK, and P38MAPK,
inhibits pro-apoptotic BCL2-associated agonist of cell death (BAD), and provoke actin reorgani-
zation. Deficiency of CDC42 enhances TCR ligation-mediated T-cell proliferation due to elevated
ERK activation, independently of Raf and MAP2K1, in the absence of CDC42 inhibition [ 222 ].