What is the structure of an Immunoglobulin (Ig)?
Unlike TCRs that can only respond to linear antigenic peptides bound to an HLA molecule, Igs (antibodies) can bind to antigens in any formation (bound, soluble, linear, complex structures). The number of antigenic determinants (epitopes) that antibodies need to be able to bind is in billions. This diversity is created by both the antibody’s structure and genetic recombination.
An Ig is composed of four polypeptide chains, two identical heavy (H) and two identical light (L) chains. Each chain has a constant (C) and variable (V) domain. There are five different H-chain C regions (isotypes): IgM (μ), IgG (γ), IgA (α), IgE (ε), IgD (δ) coded on chromosome 14. The H-chain C region determines the Ig’s ability to fix complement and to bind to Fc receptors. Th L-chains are designated kappa (κ) and lambda (λ) and coded for by chromosome 2 and 22, respectively. κ chains are used more often (65%) than λ chains.
How is antibody diversity generated?
Similar to the generation of TCR diversity, Ig genes undergo recombination. The H-chain V region genes contains three segments (V H , D H , J H ), whereas each of the L-chain genes contain two (V κ , J κ or V λ , J λ ). Each segment has several members to choose from (38-46V H , 23D H , 9J H ), (31-35V κ , 5J κ ), or (29-32V λ , 4-5J λ ). A single V(D)J is chosen from each segment and recombined by the enzymes RAG-1/RAG-2. The antigen-binding regions are formed by pairing the V domains of the L-chain to the V region of the H-chain. Within the V region of the Ig molecule are discrete regions, called complementary determining regions (CDRs), which contact the antigen specifically. Both the H- and L-chains contain three of these regions. The structure of the CDRs of an Ig is called the idiotype. The minimal antigenic determinant recognized by the CDRs is called the antigenic epitope. This process of generating Ig diversity occurs during B-cell maturation and is antigen-independent. After the B cell responds to the antigen, the BCR and Igs produced can undergo somatic mutation to increase the specificity of the antibody-binding site for the antigen.