Immunoglobulin Structure

Last modified 10/11/00.
Dr. Landry

Rm. 6055


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Glossary of Terms

antibody (immunoglobulin, Ig)
a protein that associates non-covalently with a foreign substance and initiates a process that eliminates the substance from the organism
antibody-binding site on molecule (not necessarily the antigen) that reacts with antibody
material that elicits antibody production
a small molecule that alone cannot elicit antibody production, but when attached to a larger molecule can act as an antigenic determinant and elicit antibody synthesis
Ig heavy chain (H)
larger of the two immunoglobulin chain types, approximately 50kDa in IgG, isotype (gamma, alpha, delta, epsilon or mu) determines immunoglobulin class (G, A, D, E or M, respectively)
Ig light chain (L)
smaller of the two immunoglobulin chain types, approximately 25kDa, either of two isotypes (kappa or lambda) found in all antibody classes
Fab fragment
antigen-binding fragment of Ig generated by proteolysis with papain
Fc fragment
"crystallizable" fragment of Ig generated by proteolysis with papain, mediates phagocytosis, triggers inflammation, targets Ig to particular tissues
complementarity determining regions (CDRs)
hypervariable loops in the immunoglobulin polypeptides that form the antigen binding site, 3 regions of 5-7 residues in L and 3 or 4 regions of 6-17 residues in H.

Immunoglobulin Structure

Many features of Ig structure and Antigen-antibody interaction can be examined in a kinemage.

Antibody molecules of type IgG are composed of four polypeptide chains, two identical copies of each a light chain (L) and heavy chain (H). The four chains are covalently bonded together by disulfide bonds. A small amount of N-linked carbohydrate (CHO) is attached to H. Hypervariable complementarity determining regions that determine the specificity of the antibody lie in the amino-terminal domains of L and H.

Fab and Fc fragments of IgG

Antibody functions can be separated into two proteolytic fragments by cleavage with the enzyme papain in the hinge region. The Fab fragment retains the antigen-binding activity, binding to a monovalent antigen with an affinity nearly as high as that of the entire antibody. The Fc fragment mediates class-specific functions, such as complement fixation, exhibited by IgG and IgM antibodies, in which a cascade of proteolytic activation steps (analogous to the clotting cascade) leads to lysis of the intruding cell.

The Immunoglobulin Fold

Despite their disparate functions, both Fab and Fc fragments contain domains of similar three-dimensional structure. The shared domain defines the immunoglobulin fold. The Ig fold is composed of all beta sheet secondary structure and contains one disulfide bond. L has two immunoglobulin domains, one variable (V) and one constant (C); whereas H has four domains, one variable and three constant. The variable domains are so named because antibodies of different antigen specificity have different sequences in the complementarity determining regions (CDRs) of the variable domains. The CDRs are located in loops connecting beta strands of the variable Ig domains. When L and H pair up in the antibody structure, the CDR-containing loops are brought together to form the antigen binding site.

Use the following link to view a ribbon diagram of an Fab fragment co-crystallized with its hapten. [This is an example of a catalytic antibody that was designed to have enzymatic activity. The hapten is a transition-state analog that mimics the theoretical transition state structure for enyzmatic hydrolysis of an ester linkage.]

Use the following link to view a ribbon diagram of one Fc chain co-crystallized with a fragment of an IgG-binding bacterial protein (Staphylococcus aureus protein A). Note that this fragment contains two constant immunoglobulin domains. The ability of Protein A to bind to IgG has been exploited for many years to detect the presence of antigen-antibody complexes, such as in enzyme-linked immunosorbent assays (ELISA) or Western blots. However, it is now more common to use anti-IgG produced by an heterologous organism, e.g. goat anti-rabbit IgG.

Antigen-antibody Interaction

precipitin reaction

Antibodies are divalent with respect to antigen binding and most antigens are multivalent (for example, numerous antigen molecules on a foreign cell surface); thus, a specific antigen-antibody reaction yields a crosslinked lattice that forms a precipitate. Flexibility in the hinge region of antibodies may afford a greater ability to make such multivalent contacts with different antigen materials.

features of the interface

The same types of interactions stabilize Ag-Ab binding as stabilize the folded structure of proteins, i.e., hydrophobic interactions, hydrogen bonds, van der Waals contacts, and electrostatic interactions. The two surfaces generally have complementary shapes with respect to the placement of grooves and bumps, maximizing affinity and specificity.

Immunoglobulin Class Distinctions

H type gamma; most abundant Ig; primarily found in plasma and interstitial fluid; transported across placenta; synthesis during immune response peaks 4-5 days after peak of IgM
H type alpha; with J chain forms dimer or trimer of the basic immunoglobulin structure; primarily found in mucosal secretions (intestine, sweat, saliva, tears, milk); blocks pathogen passage across endothelium

H type mu; primarily found in plasma; first to appear in immune response

H type epsilon; low abundance; important in allergy; targeted at parasites?
H type delta; low abundance; function unknown

The Immumoglobulin Superfamily of Proteins

Immunoglobulin domains occur in diverse proteins involved in the immune response. Some examples are illustrated below.

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