Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

Glossary
expresses MHC molecules presents antigens. However, dendritic cells do this particularly
efficient and are therefore sometimes dubbed `professional` antigen-presenting
cells.
Antigen-presenting cell (APC)
Term applied in particular to dendritic cells (DCs), but also a few other cell types such
as B lymphocytes. APCs express MHC class I and II molecules, and thereby present
antigens to CD4 + and CD8 + T lymphocytes. The high efficiency of antigen presentation
by DCs correlates with a high efficiency of antigen uptake and processing, high expressions
levels of the MHC molecules, co-expression of MHC class I and II molecules,
expression of various co-stimulatory molecules, a particular morphology that allows
for interactions of several T lymphocytes at the same time, an inducible mobility,
and, upon activation, tropism for lymph nodes and the capacity to localize to particular
areas of the secondary lymphatic organs to organize a cellular microenvironment
that strongly promotes interactions between the DCs and T lymphocytes of the
various types. DCs play a key role in the induction of immune responses.
Antigen processing
All steps of antigen handling inside cells that lead to the presentation of T lymphocyte
epitopes by MHC molecules. These steps include the limited proteolysis of the
antigen by endopeptidases to generate peptides and the trimming of these peptides
by exopeptidases to make them fit the MHC-binding requirements, the transport of
the peptides to the site of the biosynthesis of the MHC molecule, loading of these
molecules with the peptides, and the export of the MHC/peptide complexes for antigen
presentation at the surfaces of the cells. The pathways of antigen processing are
different for MHC class I- and II-restricted antigens. For presentation by MHC class
I molecules, antigens are reduced to peptides by the cytosolic multicatalytic proteasomes,
transported into the endoplasmic reticulum by TAP (transporter associated
with antigen processing), trimmed by exopeptidases and, assisted by various chaperones,
incorporated into nascent MHC class I molecules. Peptides for presentation by
MHC class II molecules are generated in endolysosomes and bound to prepared
MHC class II molecules. In both cases, there are indications that recycled MHC molecules
can be reloaded with new peptides. Synthetic peptides can readily be loaded
onto MHC molecules provided they fit the epitope-binding requirements. There is
an on-going debate as to where synthetic peptides are incorporated into the MHC
molecules. For some peptides, evidence has been presented for a peptide exchange
at the surface of the cells.
Apoptosis
Process of programmed cell death that ultimately leads to the disintegration of the cell.
The apoptotic remainders are readily cleared by surrounding cells in the tissue. In
contrast, in cases of necrosis the dead cells and tissues remain, and may induce inflammation
and tissue destruction. Apoptosis is under the tight control of various
regulator proteins inside the cells and at the cell surfaces. It can be induced by cell
surface receptors such as Fas or by mechanisms inside the cell such as the tumor-
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