Page 1292 - Clinical Immunology_ Principles and Practice ( PDFDrive )

1254 Part eleven Diagnostic Immunology

Antigen-presenting cell
(APC)

MHC CD80/86

CD4/CD8
TCR CD28
cSMAC
T cell APC
γ ε ε δ Fyn
TCR/CD3 MHC P P P
CD28 CD80/86 Lck P P
CD27 CD70 P P ζζ P LAT IP 3 PI3K
OX40 OX40L ZAP-70 P
4-1BB 4-1BBL PLC-γ P P
P P
P P
P Itk Ca2 + flux
pSMAC Gene transcription
T-cell activation
T cell APC
LFA-1 ICAM-1

FIG 93.1 Schematic of T-Cell Activation. T cells recognize antigen in the context of major
histocompatibility complex (MHC) molecules on antigen-presenting cells (APCs). Sustained interaction
between a T cell and APC results in the formation of the immunological synapse with membrane
reorganization and ordering of key molecules on both cells into a supramolecular activation
complex (SMAC) comprised of c (central) SMAC and p (peripheral) SMAC. Cognate interaction
with appropriate costimulatory signals results in intracellular signaling events that ultimately result
in T-cell activation. LAT, linker for activation of T cells; PLC-γ, phospholipase C-gamma; TCR, T-cell
receptor; IP3, inositol 1, 4, 5 triphosphate; P, phosphorylation; PI3K, phosphatidylinositol 3′-hydroxyl
kinase; Lck and Fyn are Src-family nonreceptor protein tyrosine kinases; Itk, IL-2–inducible T-cell
kinase; ZAP-70, ζ-chain–associated protein kinase 70. (Adapted from Figure 1, Pennock ND, et al.
Adv Physiol Educ 2013;37:273–83.)

TCR along with other costimulatory molecules and adhesion which drives T-cell proliferation in an autocrine and paracrine
receptors, which results in the formation of a large macromo- manner.
lecular structure called the supramolecular activation complex It is important to recognize that various T-cell processes and
(SMAC). The unique organization of the SMAC results in stages of differentiation are specifically regulated by metabolic
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prolonged and stronger intracellular interactions and appropriate pathways. For example, naïve T cells rely on oxidative phos-
downstream signaling activity, including phosphorylation of the phorylation for their metabolism, with additional glycolytic
CD3 receptor components. The complete culmination of the metabolism during times of proliferation. On the other hand,
TCR-induced signals results in IL-2 production and secretion, activated effector T cells demonstrate aerobic glycolysis and