Lipid Antigens

• Lipid antigens are presented to T cells by cell-surface molecules designated CD1 ("cluster of differentiation" 1).
• Antigen-presenting cells express several different forms of CD1 at their surface. Each is probably specialized to bind a particular type of lipid antigen (e.g. lipopeptide vs glycolipid).
• The exposed surface of CD1 molecules forms an antigen-binding groove much like that of MHC molecules except that
• the amino acids in the groove are more hydrophobic than those in MHC molecules.
• Like protein antigens, lipid antigens are also presented as fragments, i.e., as a "hot dog in a bun".

Polysaccharide Antigens

Some bacterial polysaccharides ingested by APCs

• can be degraded in their lysosomes
• and presented to T cells by MHC class II molecules.

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,

• kill the APC (CD8+ cytotoxic T lymphocytes [CTLs])
• carry out cell-mediated immune reactions (CD4+ Th1 cells)
• provide help to B cells (CD4+ Th2 cells)

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

• fail to provide signal two or
• transmit an as-yet-unidentified second signal that turns the T cell into a regulatory T cell (Treg) that suppresses immune responses.