chapter 35
Molecular Immunology
(Also see color figure.) HIV-1 Gpl20 peptide bound to the antigen
recognition site of an antibody Fab fragment. The binding of HIV-1
Gp 120
residues 311-318 to the antigen binding site shows the actual contacts
between antigen and antibody that underlie Ag/Ab recognition. The figure is
derived from the coordinates published in the Protein Data Bank file 1GGI.
antibody. The affinity of the antibody for the antigen is
determined by the close contact between the amino acid
residues of the antibody and the antigen. The interactions
may be electrostatic, hydrogen bonding, and apolar (van
der Waals’ interactions). Hypervariable region amino acid
residue interactions with large protein antigens occurs via
a relatively flat, large complementary surface. The spe-
cific CDR residues are commonly derived from several
of the CDRs; thus, the interaction of the antibody with
a macromolecule occurs by a discontinous and flexible
extended antigen binding site.
A three-dimensional structure of an antigen-antibody
complex in which a peptide from HIV-1 Gpl20 is bound
to a Fab fragment shows the complementarity between a
relatively small peptide antigen and the antibody. A crys-
tallographic determined structure is shown in Figure 35-9
for this antigen-antibody complex. Contacts between the
HIV peptide and the CDRs of both heavy and light chain
residues are clearly evident.
Although the binding of antigen to antibody is specific
and occurs via the variable regions of the heavy and light
chains, the binding of immunoglobulin molecules to cell
surface receptors and to some microbes is nonspecific and
occurs through binding sites within the constant regions of
the heavy chains. This part of the antibody, the Fc region,
marks the microbes for attack. Antibody that is bound
to antigen to form antigen-antibody complexes binds to
complement via determinants within the constant Fc re-
gions of the antibody molecule. Antibodies that are bound
to foreign organisms and foreign substance also signal to
phagocytes via determinants that are found on the constant
regions of the antibody. Figure 35-10 shows the structure
of the
protein, protein G, and the Fc fragment
of an antibody. Protein G and a similar protein, protein A
Staphylococcus aureus),
mask the constant region
determinants noted above and thus protect the microorgan-
isms from the immune system by preventing opsonization.
In this way thus interfere with complement activation and
block phagocytosis. This constant-region recognition of
IgGs by protein G and protein A have made them useful
tools for immobilizing antibodies for use in immunodiag-
nostic procedures and for protein purification.
Smaller differences in amino acid sequences and im-
munological properties also exist within the constant re-
gions of both the heavy and light polypeptide chains
that are unrelated to the hypervariable regions and anti-
gen recognition. The amino acid sequences within the
“constant” regions of the heavy chains are the basis for
the immunoglobulin classes. The original classification of
immunoglobulins was in terms of antibodies that distin-
guished the epitopes of the different polypeptide chain
regions; thus,
is a synonym for
The im-
munoglobulin class or isotype distinction is based on
FIGURE 35-10
(Also see color figure.) Binding of protein G
(S. aureus
) to an Fc fragment.
Protein G binding mimics the Fc receptor binding of an Ig in the Ig Fc
region. Protein G is used for purification of antibodies and in their
“capture” in immunoassays. The figure is derived from the coordinates
published in the Protein Data Bank file 1FCC.
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