HUMAN IMMUNOGLOBULIN CLASSES, SUBCLASSES, TYPES AND SUBTYPES

A. Immunoglobulin classes
The immunoglobulins can be divided into five different classes, based on differences in the amino acid sequences in the constant region of the heavy chains. All immunoglobulins within a given class will have very similar heavy chain constant regions. These differences can be detected by sequence studies or more commonly by serological means (i.e. by the use of antibodies directed to these differences).

1. IgG - Gamma  heavy chains          

2. IgM - Mu  heavy chains

3. IgA - Alpha heavy chains

4. IgD - Delta  heavy chains

5. IgE - Epsilon  heavy chains

B. Immunoglobulin Subclasses
The classes of immunoglobulins can de divided into subclasses based on small differences in the amino acid sequences in the constant region of the heavy chains. All immunoglobulins within a subclass will have very similar heavy chain constant region amino acid sequences. Again these differences are most commonly detected by serological means.

1. IgG Subclasses

a) IgG1 - Gamma 1  heavy chains

b) IgG2 - Gamma 2  heavy chains

c) IgG3 - Gamma 3  heavy chains

d) IgG4 - Gamma 4  heavy chains

2. IgA Subclasses

a) IgA1 - Alpha 1  heavy chains

b) IgA2 - Alpha 2  heavy chains

C. Immunoglobulin Types
Immunoglobulins can also be classified by the type of light chain that they have. Light chain types are based on differences in the amino acid sequence in the constant region of the light chain. These differences are detected by serological means.

1. Kappa light chains 

2. Lambda light chains 

D. Immunoglobulin Subtypes
The light chains can also be divided into subtypes based on differences in the amino acid sequences in the constant region of the light chain.

1. Lambda subtypes

a) Lambda 1 

b) Lambda 2 

c) Lambda 3 

d) Lambda 4 

E. Nomenclature
Immunoglobulins are named based on the class, or subclass of the heavy chain and type or subtype of light chain. Unless it is stated precisely you are to assume that all subclass, types and subtypes are present. IgG means that all subclasses and types are present.

F. Heterogeneity
Immunoglobulins considered as a population of molecules are normally very heterogeneous because they are composed of different classes and subclasses each of which has different types and subtypes of light chains. In addition, different immunoglobulin molecules can have different antigen binding properties because of different V_H and V_L regions.

SUBCLASSES

A.  IgG

1. Structure
The structures of the IgG subclasses are presented in Figure 7. All IgG's are monomers (7S immunoglobulin). The subclasses differ in the number of disulfide bonds and length of the hinge region.

2. Properties
Most versatile immunoglobulin because it is capable of carrying out all of the functions of immunoglobulin molecules.

a) IgG is the major Ig in serum - 75% of serum Ig is IgG

b) IgG is the major Ig in extra vascular spaces

c) Placental transfer - IgG is the only class of Ig that crosses the placenta. Transfer is mediated by receptor on placental cells for the Fc region of IgG. Not all subclasses cross equally; IgG2 does not cross well.

d) Fixes complement - Not all subclasses fix equally well; IgG4 does not fix complement

e) Binding to cells - Macrophages, monocytes, PMN's and some lymphocytes have Fc receptors for the Fc region of IgG. Not all subclasses bind equally well; IgG2 and IgG4 do not bind to Fc receptors. A consequence of binding to the Fc receptors on PMN's, monocytes and macrophages is that the cell can now internalize the antigen better. The antibody has prepared the antigen for eating by the phagocytic cells. The term opsonin is used to describe substances that enhance phagocytosis. IgG is a good opsonin. Binding of IgG to Fc receptors on other types of cells results in the activation of other functions.

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