Biomedical Engineering Reference
In-Depth Information
is required for
recruitment of the IKK complex to lipid rafts and signaling to NF-
require both DAG and Ca
2+
for activation. Nevertheless, PKC
β
B in response
to BCR ligation [74]. Thus, differences in PKC isoform utilization between BCR
and TCR pathways do not appear to correlate with functional differences in the
mechanism of NF-
κ
κ
B activation.
7.5
NF-
κ
B IN LYMPHOCYTE RESPONSES
Signaling through antigen receptors is accompanied by costimulatory signals that
modulate the resulting transcriptional response. In order to respond to antigen,
lymphocytes must undergo both proliferative (clonal expansion) as well as differ-
entiative processes. In addition, activation of antigen receptors may also induce
apoptosis, a process termed “activation induced cell death” (AICD). Thus, as in the
response of innate immune system (
Chapter 6
), the adaptive system must regulate
NF-
B in both the initiation and resolution of the effector response.
To become activated, naïve T cells must receive two distinct signals: antigen
specific and costimulatory. Antigen-specific activation signals emanate from the
binding of the TCR to cognate antigen expressed in the binding cleft of MHC.
Costimulatory signaling is provided through ligation of T cell CD28 by B7 mole-
cules expressed on activated APCs (Figure 7.6). Stimulation of naïve T cells results
κ
APC
Maturation
Costimulatory
molecules
Cytokines
CD4 Tcell
Prolifera-
tion
Bcl-2
Perforin
B7/CD28
Prolifera-
tion
Bcl-2
Cytokines
CD8 Tcell
B in the activation of naïve T cells. Naïve CD4
+
T cells are activated
following TCR recognition of antigen/MHC-II as well as costimualtion through binding of
CD28 to B7 expressed on mature antigen presenting cells (APCs). Activation of NF-
FIGURE 7.6
NF-
κ
B-
regulated genes mediates proliferation, protection from apoptosis and cytokine production in
CD4
+
T cells. Production of cytokines by T
H
1 cells provides a costimulatory signal to naïve
CD8
+
T cells that recognize their cognate antigen displayed on MHC-I. Costimulation in
CD8
+
T cells results in NF-
κ
B-dependent proliferation, protection from apoptosis, and the
production of perforin and other mediators of effector function.
κ
