1887

Chapter 6 : Antibodies

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in
Zoomout

Antibodies, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816148/9781555812461_Chap06-1.gif /docserver/preview/fulltext/10.1128/9781555816148/9781555812461_Chap06-2.gif

Abstract:

An understanding of how antibodies carry out their effector functions through interactions with other cells and soluble proteins not only has identified key features of the biology of the adaptive immune system but also has provided important and novel insights into the interactions between the innate and adaptive immune systems. Antibodies are glycoproteins and, as such, contain one or more types of carbohydrate modifications. Immunoglobulins are glycoproteins and, as such, are potent immunogens when introduced into different species, where they are recognized as ‘’foreign’’. Therefore, antibodies can be used to induce other antibodies by appropriate immunizations. The elimination of antigens is initiated by the biologic activities of antibodies, which are properties of the H-chain constant regions. Immunoglobulin G (IgG) is the most abundant Ig in serum, accounting for approximately 80% of the total of serum antibodies, with normal serum concentrations being 10 mg/ml or higher. The study of humoral immunity usually focuses on antibodies of mice and humans, and with good reason. The study of humoral immunity in cartilaginous fish has revealed the presence in the species of three classes of immunoglobulin and immunoglobulin-like proteins: IgW, nurse shark antigen receptor or new antigen receptor (NAR), and IgNARC. That IgG isotype immunoglobulins exist in nature (and that they are functional in antigen binding) suggests that, for certain species, single-chain antibodies such as NARs are sufficient to mediate protective immunity against infection.

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6

Key Concept Ranking

Major Histocompatibility Complex
0.9240484
Complement System
0.7864329
Bacterial Proteins
0.74605376
0.9240484
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 6.1
Figure 6.1

Electrophoresis of rabbit antiserum containing anti-egg albumin immunoglobulins before and after adsorption of the antibody with egg albumin. The demonstration that immunoglobulins were in the gamma globulin fraction is shown by the decreased amount of material in this fraction following removal of antibodies by adsorption. Reproduced from A. Tiselius and E. A. Kabat, 119–131, 1939, with permission.

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6.2
Figure 6.2

Fractionation of a papain digest of rabbit gamma globulin by gradient elution (sodium acetate, pH 5.5, 0.01 to 0.9 M) and carboxymethyl cellulose chromatography. Note that fractions 1 and 2 both contain Fab components, while fraction 3 is the Fc component. The different elution profiles of the Fab components reflect charge heterogeneity within the polyclonal antiserum. Adapted from R. R. Porter, 670–671, 1958, with permission.

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6.3
Figure 6.3

Separation of H and L chains from IgG antibodies by fractionation of reduced rabbit gamma globulin on Sephadex G-75 in 1 N acetic acid. Adapted from J. B. Fleischman et al., 174–180, 1962, with permission.

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6.4
Figure 6.4

Schematic diagram of an intact immunoglobulin antibody showing the variable and constant regions of the H and L chains. The CDRs, also known as the HV regions, are illustrated in the variableregion domains. Also shown are the intradomain disulfide bonds, hinge region, and associated asparaginelinked carbohydrates. Note the positions of the pepsin and papain cleavage sites relative to the interchain disulfide bonds that link the two H chains in the hinge region. Different types of diagrams typically used to represent immunoglobulin molecules. The two diagrams on the left depict each protein chain as a solid line; the two diagrams on the right emphasize the domain structure of the protein chains, representing each domain structure as either a loop or an oval. All the diagrams use the symbol s-s to represent disulfide linkages.

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6.5
Figure 6.5

Ribbon diagram of L chain in three dimensions showing the variable and constant domains.β-strands appear as flattened arrows, and shading illustrates the -strands forming the four-stranded and three-stranded sides. Numbers show amino acid positions in the variable and constant regions. The intradomain disulfide bonds stabilizing the associated four- and three-stranded sides are represented by black bars. Note the additional β-strands within the variable region. Reprinted from M. Schiffer et al., 4620–4631, 1973, with permission.

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6.6
Figure 6.6

Variability plots of the human H and L chain variable regions. Variability plots are based on the comparison of sequences of a number of different L chains and H chains In both cases sequences were aligned for maximum homology. Positions where differences in sequence length exist are identified as gaps. The VI (on the vertical axis) is a calculated value ranging from 1 (no variability at that amino acid position) to 400 (completely random use of all 20 amino acids at that position). The positions of the CDRs and FRs are identified. Adapted from T. T.Wu and E. A. Kabat, 211–240, 1970. Adapted from E. A. Kabat, , 2nd ed. (Rinehart and Winston, New York, N.Y., 1976).

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6.7
Figure 6.7

Binding sites of human myeloma protein “New” with its target antigen, vitamin K, in the antigen- binding site and of mouse myeloma McPC603 with phosphorylcholine (PC) antigen in the site The HV regions of the two antibody-binding sites are oriented in the same way, and the identity of the three major HV regions from both L and H chains are identified in the contact sites. Reprinted from D. A. Davies et al., 639–667, 1975, with permission.

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6.8
Figure 6.8

Stereo views of the binding of angiotensin II to the Fab region of a high-affinity monoclonal antibody. Side view Front view (looking into the binding site). Only the van der Waals surfaces are shown for the Fab and appear in green. The peptide hormone is shown in red. Reprinted from K. C. Garcia et al., 502–507, 1992, with permission.

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6.9
Figure 6.9

Binding sites of different antibodies to a defined antigen, lysozyme. Stereo view of antigen-combining sites of four different antilysozyme antibodies. Schematic view of these same antibodies and the epitopes recognized on the antigen. Note the excellent fit between the epitope on the antigen and the complementary antigen-binding site in the antibody For clarity, the epitopes are pulled away from the paratopes (antigen-combining sites). Reprinted from E. A. Padlan, 57–133, 1996.

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6.10
Figure 6.10

Structural changes that occur following binding of an antibody to hapten. The diagrams depict the conformation of the antigen-binding site of the antibody before and after binding to the antigen. Modified from G. J.Wedemayer et al., 1665–1669, 1997, with permission.

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6.11
Figure 6.11

Comparison of carboxy termini of the integral membrane and secreted forms of the H chains of IgM and IgG. Amino acid sequences of the transmembrane regions and cytoplasmic tails of membrane and H chains are compared with the secretory tail pieces of the secreted μ and γ H chains. The different carboxy termini result from differential splicing from a precursor RNA species. A penultimate cysteine in the secreted H chain (highlighted) is involved in the interchain disulfide bonding for production of polymeric IgM.

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6.12
Figure 6.12

Diagrams showing the modes of flexibility of IgG. Rotation around the long axis; bending to the hinge; bending between the variable and first constant region; compression; “wagging”; planar folding between Fab and Fc regions; rotation of the Fc. Comparison of the amount of flexibility around the hinge regions of the four human IgG subclasses (labeled 1, 2, 3, and 4). The straight lines show the angles that can be achieved between the two Fab arms and the Fc region. The partially circular lines indicate the potential distance traversed by the antigen-binding sites of different IgG subclasses. Segmental flexibility of immunoglobulins can facilitate antigen binding when the antigen has steric constraints, e.g., large monovalent antigens. An antibody may be capable of binding to two such large antigens simultaneously if there is sufficient flexibility between the two Fab fragments. The bottom diagram shows the antigens and antibody at lower magnification to emphasize the large relative size of the antigen. Adapted from K. H. Roux et al., 3372–3382, 1997, with permission.

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6.13
Figure 6.13

Structure of pentameric and hexameric IgM. Diagrammatic representations of IgM. The top shows the domain structure of the covalently linked IgM H and L chains, the intradomain S-S bonds, and the free Cys residues used for interchain S-S bonding between monomeric and polymeric structures. The pentamer and hexamer are schematically represented. Note that the J chain is present only in the pentameric form of IgM. Electron micrograph of IgM pentamers and hexamers. The average size of an extended IgM pentamer is 30 nanometers (nm). In this electron micrograph, 5 to 10 of the 10 binding sites of pentamers can be observed.

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6.14
Figure 6.14

Diagram of a B-cell receptor that is composed of the Ig molecule and two associated Ig-α/Ig-β complexes. The cytoplasmic tails of the Ig-αβ complexes are involved in recruitment of kinases responsible for the intracellular signal transduction following the binding of antigen to the mIg.

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6.15
Figure 6.15

Diagrams of the structures of different immunoglobulin molecules. Loops show domains that are stabilized by intradomain disulfide bonds (-S-S-). Disulfide bonds between the monomeric subunits of the two polymeric antibodies, IgM and IgA, are also shown. In each diagram, the variable domain of the L chain is amber and the variable domain of the H chain is pink.

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6.16
Figure 6.16

Structure and function of secretory IgA. Structure of dimeric IgA as found in the secretions showing the presence of secretory component, which helps protect the polymeric molecule from proteolysis. Schematic diagram showing the formation of secretory IgA by mucosal plasma cells. This dimeric IgA is bound by the poly-Ig receptor owing to the presence of J chain. The poly-Ig receptor–IgA complex is transported from the apical to the basolateral surface of the epithelial cell, where the IgA is released following the cleavage of the poly-Ig receptor. The cleaved portion of the poly-Ig receptor that remains covalently associated with IgA is the secretory component.

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6.17
Figure 6.17

Representative members of the immunoglobulin superfamily. The intrachain disulfide bonds are shown, and asparagine (N)-linked glycosylation sites are shown as spikes on the glycoproteins. V and C1 denote domains most homologous to Ig domains, whereas C2 domains are more divergent.

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555816148.chap6
1. Bengten, E.,, M. Wilson,, N. Miller,, L.W. Clem,, L. Pilstrom,, and G. W. Warr. 2000. Immunoglobulin isotypes: structure, function, and genetics.Curr. Top. Microbiol. Immunol. 248:189219.
2. Brummendorf, T.,, and V. Lemmon. 2001. Immunoglobulin superfamily receptors: cis-interactions, intracellular adapters and alternative splicing regulate adhesion. Curr. Opin. Cell Biol. 13:611618.
3. Casali, P. E.,, and W. Schettino. 1996. Structure and function of natural antibodies.Curr.Top.Microbiol. Immunol. 210:167179.
4. Crowe, J. E., Jr.,, R. O. Suara,, S. Brock,, N. Kallewaard,, F. House,, and J. H. Weitkamp. 2001. Genetic and structural determinants of virus neutralizing antibodies. Immunol. Res. 23:135145.
5. Fearon, D. T.,, and M. C. Carroll. 2000. Regulation of B lymphocyte responses to foreign and self-antigens by the CD19/CD21 complex. Annu. Rev. Immunol. 18:393422.
6. Jefferis, R.,, and J. Lund. 2002. Interaction sites on human IgGFc for Fc gamma receptors: current models. Immunol. Lett. 82:5765.
7. Johansen, F. E.,, R. Braathen,, and P. Brandtzaeg. 2000. Role of J chain in secretory immunoglobulin formation. Scand. J. Immunol. 52:240248.
8. Padlan, E. A. 1996. X-ray crystallography of antibodies. Adv. Protein Chem. 49:57133.
9. Pilstrom, L. 2002. The mysterious immunoglobulin light chain. Dev. Comp. Immunol. 26:207215.
10. Preud’homme, J. L.,, I. Petit,, A. Barra,, F. Morel,, J. C. Lecron,, and E. Lelievre. 2000. Structural and functional properties of membrane and secreted IgD. Mol. Immunol. 37:871887.

Tables

Generic image for table
Table 6.1

Fragments of antibody molecules

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Generic image for table
Table 6.2

Characteristics of antibody classes

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Generic image for table
Table 6.3

Contact area between Fab fragments and antigens

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6
Generic image for table
Table 6.4

Comparison of the effector functions of IgG subclasses of humans and mice

Citation: Corley R. 2004. Antibodies, p 113-144. In Pier G, Lyczak J, Wetzler L (ed), Immunology, Infection, and Immunity. ASM Press, Washington, DC. doi: 10.1128/9781555816148.ch6

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error