Antibody Structure and Function

CDC current flu update

Do our cells/proteins have antigens?

B Cell Receptor = Immunoglobulin (Ig) = Antibody.

Antigen binding variability = diversity is located in the variable regions of the H and L chains

Functional variability (what the antibody does after it binds antigen) is associated with the constant regions of the H chain.

Antigen receptors on B cells transmit signals to change gene expression, so the B cells proliferate and begin secreting IgM.

Serum IgM is pentameric to promote antigen agglutination (clumping) and complement activation to aid phagocytosis. Secretory (mucosal IgA) is a dimer and has a secretory piece that makes it resistant to proteolysis.

The presence of antigen-bound IgG on phagocyte FcR signals the phagocytes to engulf and kill the pathogen.

The presence of antigen-bound IgE on mast cells and eosinophils signals the cells to excrete digestive enzymes.

Structurally, the Ig isotypes all have the H₂L₂ structure.

For each of the antibody isotypes, the heavy chains on all molecules are the same (gamma, mu, delta, alpha, epsilon) and the light chains in each molecule are either all lambda or all kappa.

9. In-class activity; please bring a copy of this table. Decide if the antibodies listed on the left will bind to the immunoglobulins (antigens) listed on the right. If they do bind, think about what parts of the immunoglobulins are bound (V_H, V_L, C_H, C_L).

In addition to isotypes that identify H chains of a given species, antibodies within an isotype have small amino acid sequence differences called allotypes. It is also possible to make antibodies that recognize the specific antigen-binding regions of the V_H and V_L domains = idiotypes.

Polyclonal [anti-avian influenza H5] antibodies: Antibodies produced by several different clones of plasma cells, different clones making antibodies that bind different epitopes on H5 protein.

Monoclonal [anti-avian influenza H5] antibodies: Anrtibodies produced by a clone of identical plasma cells, all making identical antibodies that bind the same epitope on H5 protein.

In-class problems:

• a. I want an anti-human alpha chain-specific antibody. What is my antigen and what animal would I inject to get the antibody?
• b. The serum from the animal in (a) will contain many different antibodies, most NOT specific for human alpha chain. Why? How can I separate out the anti-human alpha chain antibodies? [HINT: antibodies specifically bind antigen!]
• c. I want a monoclonal mouse antibody that is specific for one particular epitope on avian influenza H5. How can I select that antibody or the plasma cell producing it?