Ganong's Review of Medical Physiology, 23rd Edition

72 SECTION ICellular & Molecular Basis for Medical Physiology

proteasomes, complexes of proteolytic enzymes that may be
produced by genes in the MHC group, and the peptide frag-
ments appear to bind to MHC proteins in the endoplasmic
reticulum. The class II MHC proteins (MHC-II proteins) are
concerned primarily with peptide products of extracellular
antigens, such as bacteria, that enter the cell by endocytosis
and are digested in the late endosomes.

T CELL RECEPTORS

The MHC protein–peptide complexes on the surface of the
antigen-presenting cells bind to appropriate T cells. There-
fore, receptors on the T cells must recognize a very wide vari-
ety of complexes. Most of the receptors on circulating T cells
are made up of two polypeptide units designated α and β.
They form heterodimers that recognize the MHC proteins and
the antigen fragments with which they are combined (Figure
3–7). These cells are called αβ T cells. About 10% of the circu-
lating T cells have two different polypeptides designated γ and
δ in their receptors, and they are called γδ T cells. These T cells
are prominent in the mucosa of the gastrointestinal tract, and
there is evidence that they form a link between the innate and
acquired immune systems by way of the cytokines they secrete
(Figure 3–3).
CD8 occurs on the surface of cytotoxic T cells that bind
MHC-I proteins, and CD4 occurs on the surface of helper T
cells that bind MHC-II proteins (Figure 3–8). The CD8 and
CD4 proteins facilitate the binding of the MHC proteins to
the T cell receptors, and they also foster lymphocyte develop-
ment, but how they produce these effects is unsettled. The

activated CD8 cytotoxic T cells kill their targets directly,

whereas the activated CD4 helper T cells secrete cytokines

that activate other lymphocytes.

The T cell receptors are surrounded by adhesion molecules

and proteins that bind to complementary proteins in the anti-

gen-presenting cell when the two cells transiently join to form

the “immunologic synapse” that permits T cell activation to

occur. It is now generally accepted that two signals are neces-

sary to produce activation. One is produced by the binding of

the digested antigen to the T cell receptor. The other is pro-

duced by the joining of the surrounding proteins in the “syn-

apse.” If the first signal occurs but the second does not, the T

cell is inactivated and becomes unresponsive.

B CELLS

As noted above, B cells can bind antigens directly, but they must

contact helper T cells to produce full activation and antibody

formation. It is the TH2 subtype that is mainly involved. Helper

T cells develop along the TH2 lineage in response to IL-4 (see

below). On the other hand, IL-12 promotes the TH1 phenotype.

IL-2 acts in an autocrine fashion to cause activated T cells to

proliferate. The role of various cytokines in B cell and T cell ac-

tivation is summarized in Figure 3–9.

The activated B cells proliferate and transform into mem-

ory B cells (see above) and plasma cells. The plasma cells

secrete large quantities of antibodies into the general circu-

lation. The antibodies circulate in the globulin fraction of

the plasma and, like antibodies elsewhere, are called

immunoglobulins. The immunoglobulins are actually the

secreted form of antigen-binding receptors on the B cell

membrane.

FIGURE 3–7 Interaction between antigen-presenting cell
(top) and αβ T lymphocyte (bottom). The MHC proteins (in this case,
MHC-I) and their peptide antigen fragment bind to the α and β units
that combine to form the T cell receptor.

β

α

+ +

β 2 mα 3

α 1 /α 2

Antigen-presenting

cell membrane

Cytoplasm

Cytoplasm

ECF

ECF

Antigen fragment

Constant regions Variable regions

T cell

membrane

T cell receptor

heterodimer (α:β)

MHC molecular

complex

S–S

FIGURE 3–8 Diagrammatic summary of the structure of

CD4 and CD8, and their relation to MHC-I and MHC-II proteins.

Note that CD4 is a single protein, whereas CD8 is a heterodimer.

Class II

MHC

CD4

TCR

CD8

TCR

Class I

MHC