• Immunoglobulins are found in large quantities in blood serum
• The gamma region contains most of the Ab in an immunized individual
• Heterogeneous

Structure of Light and Heavy Chains

• 4-chain structure
• 2 identical heavies and 2 identical lights

Light Chains

• Two types of light chains, k and l.
• the difference is in the amino acid sequence of the constant region domain
• human Ig has 60% k and 40% l

Heavy Chains

• Five different classes or isotypes of heavy chains
• each has a characteristic amino acid sequence that distinguishes it from the other four classes
• there are similarities
• the five heavy chain classes are IgA, IgD, IgE, IgG, IgM (a,d,e,g,m)
• there are some subclasses in some species. i.e. Humans have four subclasses of the IgG isotype, IgG(1-4) and two subclasses of IgA(1-2)

Domains

• there is a regularity to the structure in which there are disulfide-bridged loops or approx. 60 a.a. for each 100-110 a.a.
• There are two domains on both k and l light chains
• There are 4 or 5 domains on heavy chains

V_L or V_H domain

• the amino acid sequences in the first domain on both light and heavy chains
• highly variable
• together the V_L and V_H domains make up the Antigen binding site

C_L domain

• the other light chain domain
• constant

C_H1, C_H2, C_H3, and (for IgM and IgE) C_H4 domains

• constant domains of the heavy chains numbered from the amino terminal end

Hinge Region

• IgG, IgA, and IgD each have an exon coding for a short span of a.a. that occupies the space between the C_H1 and C_H2 domains.
• segment is rich in Cys and Pro which permits significant flexibility between the two Fab arms of the anitbody; hence hinge region
• highly susceptible to solvent

Variable Region or Variable Domain

• it has been formally proven that the amino acids comprising the hypervariable regions are the contact residues for antigen
• Complementarily-determining regions (CDRs)- they form the region of structural complementarity for Ag epitopes

Immunoglobulin Variants

IgG

• remember carbohydrate moiety is on the C_H2 domain; plays a role in cellular transport and in secretion

IgG subclasses (IgG₁, IgG₂, IgG₃, IgG₄)

• numbers are indicative of the relative concentrations of the subclasses with IgG₁ being the most abundant and IgG₄ being the least abundant in normal individuals
• Distinct Differences in the subclasses

1.     complement fixation

2.     placental transfer

3.     more later

• Structural differences

1.     the different location of the L®H  S-S bond in IgG₁ as compared to the other three classes

2.     the extended hinge region in IgG₃

3.     the 4 subclasses have about 90% a.a. homology

IgM

• are called Macroglobulin anitbodies because of their high molecular weight.
• Structural Features of IgM

1.     have an extra C_H domain as compared to IgG or IgA

2.     polymerization of the subunits into a pentamer depends on the presence of J chain whose function may be to stabilize the Fc sulfhydryl groups during Ig synthesis

3.     free molecule has a “star” or “wagon-wheel” shape when in free solution but when bound to an Antigen assumes a “crab-like shape”

4.     can have steric restriction due to lack of flexibility in the molecule.

5.     hinge region not as flexible as IgG’s

6.     IgM antibodies tend to be of relatively low affinity as measured against haptens, but, because of their multivalency, they bind with high avidity to antigens with multiple epitopes

7.     The complement binding site is in the C_H3 domain

IgA

• appears selectively in the sero-mucous secretions
• defends the exposed external surfaces of the body against attack by micro-organisms
• is present in a dimer stabilized against proteolysis by combination with another protein, secretory component.
• Important features

1.     More disulfides than IgG

2.     Two intrachain S-S on the H chain in the C_H2 and C_H3 domains which provides for intermolecular bonding and J chain binding, respectively

3.     Three glycosylated sites

• Subclasses of IgA (IgA₁ and IgA₂)

1.     IgA₁- major subclass found in serum

2.     IgA₂- major subclass found in extravascular secretions

3.     Two allotypic forms of IgA₂, the A_2m1 and A_2m2

IgD

• found only in trace conc. in serum
• primary biological role- triggering of lymphocytes
• It is co-expressed on the surface of certain subsets of lymphocytes along with IgM.
• Important features

1.     NOT secreted or synthesized by mature plasma cells

2.     The constant region of the d is longer than a or g, but shorter than e or m.

3.     Has the largest hinge region

IgE

• present in serum in trace amounts
• The Fc part of the IgE molecule has a recognition site for IgE receptors on the surface of mast cells.
• Antigen interaction with IgE Ab and Mast cells produces degranulation of mast cells.
• releases histamine and other vasoactive amines
• IgE can be thought of as the “allergy” or reaginic antibody
• Important structural features

1.     has a large number of carbohydrate moieties

2.     has five distinct domains in the H chain (like IgM)

3.     cytotrophic regions arrear to be the C_H2 and C_H3 domains

Allotypes and Idiotypes

Allotypes- structural variants of the constant regions of L or H chains of Ig that are coded in germ line genes

• are coded by Mendelian co-dominant autosomal allelic genes

Idiotypes- epitopes found in V regions of Ab molecules

Antibody Enzymes (Abzymes)

• several types of bonds are actually cleaved in an enzyme-like fashion upon reaction with antibodies specific for thos structures
• the antigen or epitope is changed after the reaction

T Cell Receptor Structure

• Heterodimer

ab Heterodimer

• conventional receptor
• Important features

1.     single a chain linked via a disulfide bond to a single b chain

2.     Intrachain disulfide bonds in both chains

3.     The two chains are very different in primary structure and they contain both common as well as clone-specific peptides

4.     Both are heavily glycosylated

5.     30-40% of the mass of the heterodimers is carbohydrate

gd Heterodimer

• small population of T cells has been IDed that does not express the ab type
• this alternative receptor is able to recognize antigen also
• It appears eary in T cell ontogeny

Tags: Abzymes, Allotypes, amino acid sequences, arbohydrate moiety, CH1, CH2, CH3, CH4, chain structure, cytotrophic regions, disulfide-bridged loops, heavy chains, Heterodimer, Idiotypes, IGa, IGd, IGe, Immunoglobulin Variants, Immunoglobulins, light chains, placental transfer, polymerization, T-cell

This entry was posted on Wednesday, March 4th, 2009 at 5:56 am and is filed under Immunology. You can follow any responses to this entry through the RSS 2.0 feed. Responses are currently closed, but you can trackback from your own site.