Basic structure of antibodies

1. The antibodies reside in the serum.

2. The early experiments of kabat and Tiselius resolved serum proteins into three major non-albumin peaks i.e. α, β, ϒ

3. Antibodies are heterodimers. They have common structure of four peptide chains.

4. The structure consists of two identical light (L) chains and two identical heavy (H) chains.

5. Molecular weight of heavy chain (H) is about 50,000.

6. The molecular weight of the light chain (L) is about 25,000.

7. H and L chains are also called immunoglobulin.

8. Each light chain is bounded to heavy chain by disulphide bonds, and other non-covalent interactions such as salt linkage, hydrogen bond etc….

9. It is sometimes called as the dimers of dimer.

10. Around first 110 (or so) AA of amino-terminal region of light or heavy chain varies greatly among antibodies of different specificity, these segments of highly variable regions are called V-regions. i.e. V_L in light chain and V_H in heavy chain.

11. The V-region has an area called complementary-determining region called as CDRs. It is this CDR (on both light and heavy chain) that constitute the antigen binding site of antigen molecule.

12. The region of relatively constant region beyond the variable region have been dubbed C regions. I.e. C_L in light chain and C_H on heavy chains, the site for attatchment of the carbohydrates are restricted to the constant region.

Heavy chain sequencing revealed five basic varieties of heavy chain

a. The sequencing of revealed that the sequence of the heavy chain are very similar to the light chain.

b. The amino terminal part constitute of 100 to 110 amino acid shows great variation among myeloma heavy chains, so were named as V- chains.

c. The remaining part of chains revealed 5 basic sequence patterns corresponding to 5 diferent heavy chain constant regions (i.e. µ, δ, γ, ε, α)

d. Each of these five different heavy chains are called an isotype.

e. The length of constant region is , approximately 330 AA in δ, ϒ, α. And approximately 440 AA in µ, ε.

f. The class of antibody is determined by the type of heavy chain present.

ANTIBODY CLASS	AA length	TYPE OF HEAVY CHAIN
IgM	440	µ
IgE	440	ε
IgG	330	ϒ
IgA	330	α
IgD	330	δ

g. A single antibody molecule may have any one type of light chain, i.e. either kappa (Κ) or lambda(λ) light chain.

h. A single antibody molecule has identical pairs of heavy and light chain respectively. i.e. H₂L₂

i. The isotypes were further classified as subisotypes (similarly were the antibodies classified).

j. In humans there are following subisotypes.

1. α à α_1, α₂ (IgA₁, IgA₂)

2. ϒàϒ₁, ϒ₂, ϒ₃, ϒ₄ (IgG₁, IgG₂, IgG₃, IgG₄)

3. The δ, ε, µ has no subisotypes.

CLASS	H-CHAIN	SUBCLASS	LIGHT CHAIN
IgM	µ	none	K or λ
IgE	ε	none	K or λ
IgG	ϒ	ϒ1, ϒ2, ϒ3, ϒ4	K or λ
IgA	α	α1, α2	K or λ
IgD	δ	none	K or λ