Antigens are macromolecules that elicit an immune response in the body. Antigens can be

• proteins
• polysaccharides
• conjugates of lipids with
  • proteins (lipoproteins) and
  • polysaccharides (glycolipids).

Most of this page will describe how protein antigens are presented to the immune system.

The presentation of lipid and polysaccharide antigens will be mentioned at the end. [Link]

It will be helpful to distinguish between

• antigens that enter the body from the environment; these would include
  • inhaled macromolecules (e.g., proteins on cat hairs that can trigger an attack of asthma in susceptible people)
  • ingested macromolecules (e.g., shellfish proteins that trigger an allergic response in susceptible people)
  • molecules that are introduced beneath the skin (e.g., on a splinter or in an injected vaccine)
  
• antigens that are generated within the cells of the body; these would include
  • proteins encoded by the genes of viruses that have infected a cell
  • aberrant proteins that are encoded by mutant genes; such as mutated genes in cancer cells

In all cases, however, the initial immune response to any antigen absolutely requires that the antigen be recognized by a T lymphocyte ("T cell"). The truth of this rule is clearly demonstrated in AIDS: the infections (viral or fungal or bacterial) that so often claim the life of AIDS patients do so when the patient has lost virtually all of his or her CD4+ T cells.

The two categories of antigens are processed and presented to T cells by quite different mechanisms.

First Group: Exogenous antigens

Exogenous antigens (inhaled, ingested, or injected) are taken up by antigen-presenting cells (APCs). These include:

• phagocytic cells like dendritic cells and macrophages;
• B lymphocytes ("B cells"); which are responsible for producing antibodies against the antigen.

Antigen-presenting cells

• engulf the antigen by endocytosis.
• The endosome fuses with a lysosome where the antigen is
• degraded into fragments (e.g. short peptides).
• These antigenic peptides are then displayed at the surface of the cell nestled within a
• class II histocompatibility molecule.
• Here they may be recognized by CD4+ T cells.

(Dendritic cells can also present intact antigen directly to B cells. In this case, the engulfed antigen is not degraded in lysosomes but is returned to the cell surface for presentation to B cells bearing BCRs of the appropriate specificity.)

Second Group: Endogenous antigens

Antigens that are generated within a cell (e.g., viral proteins in any infected cell) are

• degraded into fragments (e.g., peptides) within the cell and
• displayed at the surface of the cell nestled within a
• class I histocompatibility molecule.
• Here they may be recognized by CD8+ T cells.
• Most CD8+ T cells are cytotoxic.
• They have the machinery to destroy the infected cell (often before it is able to release a fresh crop of viruses to spread the infection). [Link to discussion.]

Now for more details.

The Class I Pathway

Class I histocompatibility molecules are transmembrane proteins expressed at the cell surface. Like all transmembrane proteins, they are synthesized by ribosomes on the rough endoplasmic reticulum (RER) and assembled within its lumen. There are three subunits in each class I histocompatibility molecule:

• the transmembrane polypeptide (called the "heavy chain")
• the antigenic peptide
• beta-2 microglobulin