Molecular Immunology
IgG, IgE, IgD
“ component
J chain
F I G U R E 3 5 -1 1
(Also see color figure; color coding is as the same as indicated in Fig. 35-7.) Immunoglobulin classes. The five
immunoglobulin classes are determined by the amino acid sequences of the constant regions of the heavy
polypeptide chains (see Table 35-2).
Antigen-Antibody Reactions
Under normal circumstaces an animal produces a mix-
ture of antibodies because of there being several epitopes
of an antigen. This is because antibodies that react with
the different epitopes of the same antigen are produced
by many different B-cell clones (see “B-Cell Clonal Se-
lection and Proliferation”). Each B-cell clone synthesizes
antibodies to a single epitope and thus the total antibody
that is specific for the antigen will be a mixture of single-
clone-derived antibodies. The total antibody is there-
fore polyclonal with the antibody molecules from each
clone recognizing different epitopes on the same antigen
The two Fab “arms” of the reference immunoglobulin
molecule, each with the ability to recognise antigen, make
the antibody molecule bivalent or divalent. The bivalent
immunoglobulin molecules are IgG, IgA, IgE, IgD. IgM
molecules, as described above, are decavalent and can
react with as many as 10 antigen molecules. One form of
IgA can bind four antigen molecules. The consequence
of bivalency and multivalency is that antibodies can
react with antigens to form aggregates composed of
alternating Ag-Ab-Ag-Ab molecules. This cross-linking
results in the formation of large Ag-Ab aggregates.
Such cross-linking is strictly true only for polyclonal
antibodies, i.e., mixtures of monoclonal antibodies that
contain antibodies to more than a single epitope on the
antigen. If an antigen molecule possesses two copies
of the epitope that the monoclonal Ab recognizes, then
monoclonal antibodies can cross-link also.
The Ag-Ab aggregates may become sufficiently large so
that solutions become visibly turbid. The complexes can
precipitate from the solution. This phenomenon is called
and is the basis of many antibody-
based diagnostic tests. It is used to deplete plasma samples
of a particular protein. Immuno-absorbed plasmas find
widespread use in tests of specific coagulation factors.
The formation of aggregates of red blood cells that oc-
curs when cells of one blood type are mixed with plasma
from an individual of a different blood type is another
example of Ab-Ab cross-linking. Red blood cell aggrega-
tion and precipitation is the basis for blood typing and
cross-matching procedures of immunohematology. The
formation of bands in gels using immunoelectrophoresis
or immunodiffusion procedures involves laboratory meth-
ods that exploit the property of bivalency (or multivalency)
of immunoglobulins.
Because of the bi- and multivalency of antibodies, the
formation of antigen-antibody aggregates is sensitive to
concentrations of antigen and antibody. Op-
timal precipitation occurs at a concentration called the
equivalence point. At too high an antigen concentration,
the binding of antigen molecules to antibody is saturated
and the aggregates become simple complexes between
each antibody and the two antigens. At too high an an-
tibody concentration, all of the antibody binding sites
on the antigen are occupied by individual antibodies and
sites are not available to form cross-links. The complexes
that contain either excess antigen or excess antibody are
usually soluble and thus do not lead to identification of
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