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

382 Glossary
tion to the variable domain, consists of three constant domains in the case of IgG,
IgD and IgA or four in the case of IgE and IgM. In the case IgE and IgA these tetramers
may form dimers. IgM is a pentamer of the basic dimeric unit. The B lymphocytes
that express specific antibodies can efficiently bind antigen and process it for
presentation to helper T cells. They are thereby efficient antigen-presenting cells for their
cognate antigen. Soluble-form antibodies bind and neutralize pathogens carrying
the corresponding antigen, opsonize the antigen or antigen-bearing particle, and,
thus, prepare it for specific phagocytosis and degradation by macrophages or serve as
adaptor molecules that link antigen specificity to the antibody-dependent effector
mechanisms of the immune system, such as complement and antibody-dependent cellular
cytotoxicity. The type of immune effector function addressed is determined by
the particular constant domains of the antibodies.
Antibody-dependent cellular cytotoxicity (ADCC)
Destruction of target cells that are coated with a specific antibody by Fc receptor-expressing
cytolytic cells. Fc receptors bind the constant region of the antibody. The effector
cells in this context can be cytotoxic T lymphocytes and natural killer cells, but also
macrophages or neutrophils. For cancer therapy, the application of antibodies with
specificity for a molecule expressed at the surface of the tumor cells is meant to recruit
Fc receptor-positive effector cells, leading to their activation and the destruction
of the tumor cells. Examples for such therapeutic antibodies are anti-CD25 (interleukin-2
receptor) in cases of T cell lymphoma and anti-CD20 in cases of B lymphocyte
lymphoma.
Antigen
Any compound bound specifically by antigen receptors of the immune system, i. e.
antibodies and T cell receptors. Whereas antibodies can be induced against molecules
of virtually any chemical class, antigens recognized by T lymphocytes are almost exclusively
proteins. Antibodies usually bind the entire molecule ± in the case of proteins,
the epitopes may be continuous stretches of the protein sequence (continuous
epitopes) or combinations of elements contributed by different segments of the primary
sequence of the protein (discontinuous epitopes). Epitopes for T lymphocytes
are peptides generated inside the cells by limited proteolysis from the antigen,
bound selectively by the MHC molecules and displayed as peptide/MHC complexes
at the cell surfaces. The peptides for presentation by MHC class I molecules are
mostly 8±9 amino acids; those for presentation by MHC class II molecules are
mostly 11±15 amino acids long.
Antigen presentation
Display of MHC-bound peptides at the surface of the cells for recognition by the T
cell receptor. The MHC molecules select from a pool of peptides generated by limiting
proteolysis inside the cells from antigen peptides that fulfill MHC allele-specific
binding requirements. The MHC molecules come in two classes ± MHC class I molecules
present peptides for recognition by CD8 + T lymphocytes and MHC class II
molecules present peptides for recognition by CD4 + T lymphocytes. Every cell that