Defense Mechanisms of the Body
661
The function of the macrophage (or dendritic cell) as an
APC for helper T cells is easier to visualize (
Figure 18–11a
)
because the macrophage forms a link between nonspecifi c and
specifi c immune defenses. After a microbe or noncellular anti-
gen has been phagocytized by a macrophage in a
nonspecifi
c
response, it is partially broken down into smaller peptide frag-
ments by the macrophage’s proteolytic enzymes. The result-
ing digested fragments then bind (within endosomes) to class
II MHC proteins synthesized by the macrophage. The frag-
ments actually fi t into a deep groove in the center of the MHC
proteins. The fragment-MHC complex is then transported to
the cell surface, where it is displayed in the plasma membrane.
It is to this entire complex on the cell surface of the macro-
phage (or dendritic cell) that a specifi c helper T cell binds.
Note that it is not the intact antigen but rather the pep-
tide fragments, called antigenic determinants or
epitopes,
of
the antigen that are complexed to the MHC proteins and pre-
sented to the T cell. Despite this, it is customary to refer to
“antigen” presentation rather than “epitope” presentation.
How B cells process antigen and present it to helper T cells
is essentially the same as just described for macrophages (
Figure
18–11b
). It must be emphasized that the ability of B cells to
present antigen to helper T cells is a
second
function of B cells in
response to antigenic stimulation, the other being the differen-
tiation of the B cells into antibody-secreting plasma cells.
The binding between helper T-cell receptor and an anti-
gen bound to class II MHC proteins on an APC is the essen-
tial
antigen-specifi
c
event in helper T-cell activation. However,
this binding by itself will not result in T-cell activation. In
addition,
nonspecifi
c
interactions occur between other (nonan-
tigenic) pairs of proteins on the surfaces of the attached helper
T cell and APC, and these provide a necessary
costimulus
for
T-cell activation (
Figure 18–12
).
Finally, the antigenic binding of the APC to the T cell,
along with the costimulus, causes the APC to secrete large
amounts of the cytokines
interleukin 1 (IL-1)
and
tumor
necrosis factor (TNF),
which act as paracrine agents on the
Class II MHC
protein
Macrophage
Helper T-cell
receptor
Antigen
Immunoglobulin
(B-cell receptor)
B Cell
Antigen
Class II MHC
protein
Helper T-cell
receptor
Class II MHC
protein
(a)
Class II MHC
protein
Antigen
fragment
Helper T Cell
Nucleus
Helper T Cell
Nucleus
(b)
Begin
Begin
Figure 18–11
Sequence of events by which antigen is processed and presented to a helper T cell by (a) a macrophage or (b) a B cell. In both cases, begin the
fi gure with the antigen in the extracellular fl
uid.
Adapted from Gray, Sette, and Buus.
2
1
3
Helper
T-cell
receptor
Helper T Cell
Class II
MHC protein
IL-1
TNF
Nonantigenic
matching
proteins
(see Figure 18-11)
Antigen-presenting cell
Figure 18–12
Three events are required for the activation of helper T cells:
(1) presentation of the antigen bound to a class II MHC protein
on an antigen-presenting cell (APC); (2) the binding of matching
nonantigenic proteins in the plasma membranes of the APC and
the helper T cell (costimulus); and (3) secretion by the APC of the
cytokines interleukin 1 (IL-1), tumor necrosis factor (TNF), and
other cytokines, which act on the helper T cell.
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