7.

ANTIGEN PRESENTATION

Q. Which other receptors have ITIMs?

A. The inhibitory Fc receptor FcRIIb expressed on B cells has
ITIMs (see Fig. 3.20). Other inhibitory receptors with similar
motifs include the killer inhibitory receptors (KIRs) expressed on
NK cells as well as T cells (see Figs 10.3 and 10.5).

Interleukin-2 drives T cell division

Apart from the cell surface interactions, cytokines, acting

locally, are required for promoting T cell division (see
Fig. 7.18).
Triggering of the TCR along with co-receptors results
in IL-2 synthesis by the T cell itself. In most CD4+ cells
and some CD8+ T cells, there is a transient production of
IL-2 for 12 days. During this time the interaction of IL2 with the high-affinity IL-2R results in T cell division.
On resting T cells, the IL-2R is predominantly present
as a low-affinity form consisting of two polypeptide
chains, a chain (p75) that binds IL-2 and a chain that
signals to the cell. When the T cell is activated, it produces an chain (p55 = CD25), which contributes to IL2 binding and, together with the and chains, forms the
high-affinity receptor (Fig. 7.23).
The transient expression of the high-affinity IL-2R for
about 1 week after stimulation of the T cell, together with
the induction of CTLA-4, helps limit T cell division. In
the absence of positive signals, the T cells will start to die
by apoptosis.
An understanding of the requirements for T cell
division has allowed researchers to generate long-lived T
cell lines, which are used in many areas of immunological
research (Method Box 7.2).

Other cytokines contribute to activation and

division

Other cytokines may also contribute to T cell proliferation. For example, IL-1 and IL-6 induce the expression
of IL-2R on resting T cells.
Q. Which cells generate IL-1 and IL-6?
A. Mononuclear phagocytes among others. Thus the production of these cytokines enhances their antigen-presenting
function.

Additionally IL-4 and IL-15 may provide stimulatory

signals through their own receptors.
IL-12 is also of major importance in T cell activation:
helping to enhance IFN production; and
directing naive T cells to develop into TH1 cells.
IL-15 made by APCs can also induce T cell proliferation
and may be very important before IL-2 is produced.

ANTIGEN PRESENTATION AFFECTS THE

COURSE OF AN IMMUNE RESPONSE

APCs may be activated rapidly in an immune response, for

example by:
the immunogenic entity itself, in the case of bacteria
and some viruses; or
the antigen in conjunction with the adjuvant component of a vaccine.

160

METHOD BOX 7.2

T cell lines

To test the response of lymphocytes to a specific antigen that

is being presented, the lymphocyte stimulation test (Fig. 1)
may be used. This test measures the response of the T cells
to antigen as indicated by their entering the cell cycle and
incorporating precursors of DNA synthesis.

The lymphocyte stimulation test

culture
medium
antigen
suspension

3Hthymidine

lymphocytes
whole
blood
and
saline

centrifugation

glass fiber
filter

Ficoll
Isopaque
separated
blood

cultivation

measure
radioactivity

Fig. 1 In the lymphocyte stimulation test, whole blood in

saline solution is first layered on Ficoll Isopaque (which has a
density between, and therefore separates, white cells and red
cells) and centrifuged (400 g). This separates the
lymphocytes from the other cell and serum constituents. The
cells are washed (to remove contaminants such as antigen)
and then put into test tubes with a suspension of antigen and
culture medium. Tritiated thymidine (3H-thymidine) is added
16 hours before the cells are harvested. The cells are
harvested on a glass-fiber filter disk and their radioactivity
measured by placing the disk in a liquid scintillation counter.
A high count indicates that the lymphocytes have undergone
transformation and confirms their responsiveness to the
antigen. This test can also be used for cells from lymphoid
tissue.

Antigen presentation is not a unidirectional process. T

cells, as they become activated:
release cytokines such as IFN and granulocyte
macrophage colony stimulating factor (GMCSF);
express surface molecules such as CD40 ligand, which
enhance antigen presentation.
When APCs are activated, they express more MHC class
I and II molecules, Fc receptors, and co-stimulatory
adhesion molecules, including B7-1 and B7-2, CD11a/b/c,
ICAM-1, and ICAM-3. They also produce numerous
cytokines (e.g. IL-1, IL-6, TNF), enzymes, and other
mediators.
Activation of lymphocytes leads to two partially
competing processes:
cell proliferation; and
cell differentiation into effector cells.