PART II

The recognition of antigen

4 Antigen Recognition by B-cell and T-cell Receptors

5 The Generation of Lymphocyte Antigen Receptors
6 Antigen Presentation to T Lymphocytes

Antigen Recognition by
B-cell and T-cell Receptors 4
Innate immune responses are the body’s initial defense against infection, but IN THIS CHAPTER
these work only to control pathogens that have certain molecular patterns or The structure of a typical antibody
that induce interferons and other nonspecific defenses. To effectively fight molecule.
the wide range of pathogens an individual will encounter, the lymphocytes of
the adaptive immune system have evolved to recognize a great variety of dif- The interaction of the antibody
ferent antigens from bacteria, viruses, and other disease-causing organisms. molecule with specific antigen.
An antigen is any molecule or part of a molecule that is specifically recognized Antigen recognition by T cells.
by the highly specialized recognition proteins of lymphocytes. On B cells these
proteins are the immunoglobulins (Igs), which these cells produce in a vast
range of antigen specificities, each B cell producing immunoglobulins of a
single specificity (see Section 1-12). A membrane-bound form of immuno­
globulin on the B-cell surface serves as the cell’s receptor for antigen, and is
known as the B-cell receptor (BCR). A secreted form of immunoglobulin of
the same antigen specificity is the antibody produced by terminally differenti-
ated B cells—plasmablasts and plasma cells. The secretion of antibodies, which
bind pathogens or their toxic products in the extracellular spaces of the body
(see Fig. 1.25), is the main effector function of B cells in adaptive immunity.
Antibodies were the first proteins involved in specific immune recognition to
be characterized, and are understood in great detail. The antibody molecule
has two separate functions: one is to bind specifically to the pathogen or its
products that have elicited the immune response; the other is to recruit other
cells and molecules to destroy the pathogen once antibody has bound. For
example, binding by antibodies can neutralize viruses and mark pathogens
for destruction by phagocytes and complement, as described in Chapters 2
and  3. Recognition and effector functions are structurally separated in the
antibody molecule, one part of which specifically binds to the antigen whereas
the other engages the elimination mechanisms. The antigen-binding region
varies extensively between antibody molecules and is known as the variable
region or V region. The variability of antibody molecules allows each anti-
body to bind a different specific antigen, and the total repertoire of antibodies
made by a single individual is large enough to ensure that virtually any struc-
ture can be recognized. The region of the antibody molecule that engages the
effector functions of the immune system does not vary in the same way and

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 The structure of a typical antibody molecule. 145

(Micrograph ×300,000) Angle between arms is 60o Angle between arms is 90o

Immunobiology | chapter 4 | 04_004

4-5 et alThe
Murphy | Ninthhinge
edition region
of the immunoglobulin molecule allows Fig. 4.5 Antibody arms are joined by
© Garland Science design by blink studio limited a flexible hinge. An antigen consisting
flexibility in binding to multiple antigens.
of two hapten molecules (red balls
in diagrams) that can cross-link two
The hinge region between the Fc and Fab portions of the IgG molecule allows antigen-binding sites is used to create
for some degree of independent movement of the two Fab arms. For exam- antigen:antibody complexes, which can
ple, in the antibody molecule shown in Fig. 4.1a, not only are the two hinge be seen in the electron micrograph. Linear,
regions clearly bent differently, but the angle between the V and C domains triangular, and square forms are seen, with
in each of the two Fab arms is also different. This range of motion has led to short projections or spikes. Limited pepsin
the junction between the V and C domains being referred to as a ‘molecular digestion removes these spikes (not shown
in the figure), which therefore correspond to
ball-and-socket joint.’ This flexibility can be revealed by studies of antibodies
the Fc portion of the antibody; the F(abʹ)2
bound to small antigens known as haptens. These are molecules of various pieces remain cross-linked by antigen. The
types that are typically about the size of a tyrosine side chain. Although hap- interpretation of some of the complexes is
tens are specifically recognized by antibody, they can stimulate the produc- shown in the diagrams. The angle between
tion of anti-hapten antibodies only when linked to a protein (see Appendix I, the arms of the antibody molecules varies.
Section A-1). Two identical hapten molecules joined by a short flexible region In the triangular forms, this angle is 60°,
can link two or more anti-hapten antibodies, forming dimers, trimers, tetra­ whereas it is 90° in the square forms,
showing that the connections between
mers, and so on, which can be seen by electron microscopy (Fig. 4.5). The the arms are flexible. Photograph courtesy
shapes formed by these complexes show that antibody molecules are flexible of N.M. Green.
at the hinge region. Some flexibility is also found at the junction between the
V and C domains, allowing bending and rotation of the V domain relative to
the C domain. Flexibility at both the hinge and the V–C junction enables the
two arms of an antibody molecule to bind to sites some distance apart, such
as the repeating sites on bacterial cell-wall polysaccharides. Flexibility at the
hinge also enables antibodies to interact with the antibody-binding proteins
that mediate immune effector mechanisms.

Summary.

The IgG antibody molecule is made up of four polypeptide chains, comprising

two identical light chains and two identical heavy chains, and can be thought
of as forming a flexible Y-shaped structure. Each of the four chains has a varia-
ble (V) region at its amino terminus, which contributes to the antigen-binding
site, and a constant (C) region. The light chains are bound to the heavy chains
by many noncovalent interactions and by disulfide bonds, and the V regions of
the heavy and light chains pair in each arm of the Y to generate two identical
antigen-binding sites, which lie at the tips of the arms of the Y. The possession
of two antigen-binding sites allows antibody molecules to cross-link antigens
and to bind them much more stably and with higher avidity. The trunk of the
Y, also called the Fc fragment, is composed of the carboxy-terminal domains
of the heavy chains, and it is these domains that determine the antibody’s
isotype. Joining the arms of the Y to the trunk are the flexible hinge regions.
The Fc fragment and hinge regions differ in antibodies of different isotypes.

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