Antigen Presentation

Index to this page
Antigens are macromolecules that elicit an immune response in the body. Antigens can be

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

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: Antigen-presenting cells

(Dendritic cells and macrophages 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 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.
(See Protein Kinesis for further details.)
There are three subunits in each class I histocompatibility molecule:
See Histocompatibility Molecules
Link to model of a human class I
histocompatibility molecule (92K)

All of these must be present within the lumen of the endoplasmic reticulum if they are to assemble correctly and move through the Golgi apparatus to the cell surface.

The Problem: proteins encoded by the genes of an infecting virus are synthesized in the cytosol. How to get them into the endoplasmic reticulum?

The Solution: TAP (= transporter associated with antigen processing).
External Link
Link to animation of the class I pathway (requires Flash plug-in).
Please let me know by e-mail if you find a broken link in my pages.)

The Class II Pathway

Class II histocompatibility molecules consist of

All three components of this complex must be present in the endoplasmic reticulum for proper assembly.

But antigenic peptides are not transported to the endoplasmic reticulum, so a protein called the invariant chain ("Ii") temporarily occupies the groove.

The steps: Meanwhile, Then,
Link to discussion of how TCRs are synthesized.

Interconnections Between the Class I and Class II Pathways

Cross-Presentation: Transferring Exogenous Antigens to the Class I Pathway

Cross-presentation is the transferring of extracellular antigens like bacteria, some tumor antigens, and antigens in cells infected by viruses into the class I pathway for stimulation of CD8+ cytotoxic T cells (CTL). Only certain "professional" antigen-presenting cells (APCs) like dendritic cells can do this; that is, use the class I as well as the class II pathways of antigen presentation.

Cross-presentation following infection by viruses is important because:

However, when an infected cell dies, it can be engulfed by a professional APC, and the antigens within it can enter the class I pathway. One mechanism:

Diverting Antigens from the Class I to the Class II Pathway

Autophagy [Link] provides a mechanism by which cells can transfer endogenous (intracellular) antigens into the class II pathway, for example

B Lymphocytes: A Special Case

B lymphocytes are both antigen-receiving and antigen-presenting cells. They bind intact antigens (e.g., virus particles, proteins) with their B cell receptor (BCR). They can come in contact with these antigens by

B lymphocytes process antigen by the class II pathway for presentation to T cells.

The process:
Graphic showing the steps leading to antibody secretion

Lipid and Polysaccharide Antigens

Lipid Antigens

Polysaccharide Antigens

Some bacterial polysaccharides ingested by APCs

Nitric oxide (NO) appears to be essential for this process.

Costimulation

The binding of a T cell to an antigen-presenting cell (APC) is by itself not enough to activate the T cell and turn it into an effector cell: one able to, for examples,

In order to become activated, the T cell must not only bind to the epitope (MHC-peptide) with its TCR but also receive a second signal from the APC. The receipt of this second signal is called costimulation. Among the most important of these costimulators are molecules on the APC designated B7 and their ligand on the T cell designated CD28. The binding of CD28 to B7 provides the second signal needed to activate the T cell.

Although T cells may encounter self antigens in body tissues, they will not respond unless they receive a second signal. In fact, binding of their TCR ("signal one") without "signal two" causes them to self-destruct by apoptosis. Most of the time, the cells presenting the body's own antigens either In either case, self-tolerance results.
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9 July 2013