Determinants recognized by T cells

Composition
Antigenic determinants recognized by T cells are created by the primary sequence of amino acids in proteins. T cells do not recognize polysaccharide or nucleic acid antigens. This is why polysaccharides are generally T-independent antigens and proteins are generally T-dependent antigens. The determinants need not be located on the exposed surface of the antigen since recognition of the determinant by T cells requires that the antigen be proteolytically degraded into smaller peptides. Free peptides are not recognized by T cells, rather the peptides associate with molecules coded for by the major histocompatibility complex (MHC) and it is the complex of MHC molecules + peptide that is recognized by T cells.

Size
In general antigenic determinants are small and are limited to approximately 8-15 amino acids.

Number
Although, in theory, each 8-15 residues can constitute a separate antigenic determinant, in practice, the number of antigenic determinants per antigen is much less than what would theoretically be possible. The antigenic determinants are limited to those portions of the antigen that can bind to MHC molecules. This is why there can by differences in the responses of different individuals.

SUPERANTIGENS

When the immune system encounters a conventional T-dependent antigen, only a small fraction (1 in 10⁴ -10⁵) of the T cell population is able to recognize the antigen and become activated (monoclonal/oligoclonal response). However, there are some antigens which polyclonally activate a large fraction of the T cells (up to 25%). These antigens are called superantigens (Figure 5).

Examples of superantigens include: Staphylococcal enterotoxins (food poisoning), Staphylococcal toxic shock toxin (toxic shock syndrome), Staphylococcal exfoliating toxins (scalded skin syndrome) and Streptococcal pyrogenic exotoxins (shock). Although the bacterial superantigens are the best studied there are superantigens associated with viruses and other microorganisms as well.

The diseases associated with exposure to superantigens are, in part, due to hyper activation of the immune system and subsequent release of biologically active cytokines by activated T cells.

7. Discuss the general properties of all immunoglobulins; Describe the basic structure of immunoglobulins;

Immunoglobulins are glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies. The immunoglobulins derive their name from the finding that they migrate with globular proteins when antibody-containing serum is placed in an electrical field

BASIC STRUCTURE OF IMMUNOGLOBULINS

The basic structure of the immunoglobulins is illustrated in figure 2. Although different immunoglobulins can differ structurally, they all are built from the same basic units.

Heavy and Light Chains
All immunoglobulins have a four chain structure as their basic unit. They are composed of two identical light chains (23kD) and two identical heavy chains (50-70kD)

Disulfide bonds

Inter-chain disulfide bonds
The heavy and light chains and the two heavy chains are held together by inter-chain disulfide bonds and by non-covalent interactions The number of inter-chain disulfide bonds varies among different immunoglobulin molecules.

Intra-chain disulfide binds
Within each of the polypeptide chains there are also intra-chain disulfide bonds.

Variable (V) and Constant (C) Regions
When the amino acid sequences of many different heavy chains and light chains were compared, it became clear that both the heavy and light chain could be divided into two regions based on variability in the amino acid sequences. These are the:

Light Chain - V_L (110 amino acids) and C_L (110 amino acids)

Heavy Chain - V_H (110 amino acids) and C_H (330-440 amino acids)

Hinge Region
This is the region at which the arms of the antibody molecule forms a Y. It is called the hinge region because there is some flexibility in the molecule at this point.

Domains
Three dimensional images of the immunoglobulin molecule show that it is not straight as depicted in figure 2A. Rather, it is folded into globular regions each of which contains an intra-chain disulfide bond (figure 2B-D). These regions are called domains.

Light Chain Domains - V_L and C_L

Heavy Chain Domains - V_H, C_H1 - C_H3 (or C_H4)

Oligosaccharides
Carbohydrates are attached to the C_H2 domain in most immunoglobulins. However, in some cases carbohydrates may also be attached at other locations.

8. Describe the structures and properties of immunoglobulin classes; Explain the structural basis for immunoglobulin isotypes, allotypes and idiotypes;

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

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

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.

Kappa light chains

Lambda light chains

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.

Lambda subtypes

a) Lambda 1

b) Lambda 2

c) Lambda 3

d) Lambda 4

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 should assume that all subclass, types and subtypes are present. IgG means that all subclasses and types are present.

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.