Structural Biochemistry/Protein function/Antigen

Antigen is a macromolecule that causes an immune response by lymphocytes. Antigen receptor, a surface protein located on B cells and T cells, binds to antigens and initiates acquired immune responses. The antigen receptors on B cells are called B cell receptors (or membrane immunoglobulins) and the antigen receptors on T cells are called T cell receptors.



Antigens may either be proteins or polysaccharides. In general, an antigen is defined as a substance that binds to specific antibodies, which in the human body are used to find and neutralize any potentially harmful foreign substances in the bloodstream. The specific binding between antigen and antibody is similar to that of the lock-and-key binding model.

In human blood, the different lettering of different blood types is designated by the specific antigen present in the individual's blood cells. While all types contain the oligosaccharide (O) antigen, the A and B blood types are defined by having N-acetylgalactose (A) or galactose (B) monosaccharide. Likewise, the AB blood group has both A and B antigens. Additional antigens are bound to define the positive or negative state of the ABO blood groups. The structures of the enzymes that bind to the antigen are similar and very slightly different, demonstrating antigen specificity.

Applications
Besides being used in the indirect ELISA technique to detect the presence of antibody, antigens can also be used to prepare vaccines to establish or to improve immunity to a particular disease.

When pathogens get into the blood and lymph, antigens on the surfaces of the pathogens stimulate lymphocytes to produce specific antibodies which kill the pathogens by lysis, enhanced phagocytosis, clumping the pathogen together, or neutralizing the toxins from pathogens.

In wake of first (primary response) infection involving a particular antigen, the responding naive cells proliferate to produce a colony of cells, most of which transform into plasma cells or effector B cells (which produce the antibodies) to resolve the infection, and the rest persist as the memory cells that can survive for years, or indeed even for a lifetime. This is a complicated set of reactions that needs a latent period for the production of antibodies.

During the invasion of the same type of pathogens, however, previously produced memory cells trigger lymphocytes to produce much a larger amount of antibodies immediately. Unlike antibodies produced in the primary response that can only be maintained for a short period of time, the antibodies produced in the secondary response can be maintained for a longer period, usually for years.

Knowing these facts, vaccines are made to stimulate the production of memory cells to get one ready for the exposure to that kind of pathogens in the future.



Levels of antibodies produced during the primary response and secondary response

There are three types of antigen-based vaccines, namely, purified, recombinant, and synthetic.

Purified antigen vaccines, sometimes called subunit vaccines,composed small fragments of molecules purified directly from the pathogen that generates a "protective" immune response. These molecules can be proteins, polysaccharides or exotoxins (i.e. bacterial proteins either chemically inactivated or attenuated (derived from mutated organisms) to prevent toxicity in the host.)

Example: Vaccines against causative agents of meningitis in children

Recombinant antigen vaccines are immunogenic proteins produced by genetic engineering. DNA encoding for an immunogenic protein of a pathogen can be inserted into either bacteria, yeast, viruses which infect mammalian cells, or by transfection of mammalian cells. The cells will then produce the protein endogenously and the protein can be harvested.

Example: surface protein of Hepatitis B virus (HBsAg)

Synthetic Antigen Vaccines are peptide antigens synthesized by automated machines. Synthetic polynucleotide technology also exists while synthetic polysaccharide technology is still under development. Which sequences to choose requires knowledge of the conformational structures for B cell epitopes (sequential v. assembled) and of the anchor residues of MHC for T cell epitopes. Computer algorithms are available to assist in selection, but trial-and-error approach is still required. Other aids include the generation of "protective" monoclonal Abs (B cell epitopes & phage-display libraries) and the peptide-dependent restimulation of T cells from convalescent subjects (T cell epitopes).

Reference: Body Defense Mechanisms for A & H Levels, by Pang King Chee, HKASME