Biology Reference
In-Depth Information
T A B L E
11.2. Differential Expression of Receptors During the Two DC Life
Cycles
Immature DC
Mature DC
Phagocytic molecules
Antigen presentation molecules
DEC-205
MHC Class I and II
Macrophage mannose receptor
Stimulatory molecules
Fc receptor
CD80, CD86, CD83
Complement receptor
Adhesion molecules
Antigen processing/loading molecules
DC-SIGN (CD209)
HLA-DM
ICAM-1 (CD54)
Proteases
p150,95 (CD11c)
DC-LAMP
Adhesion/migration molecules
DC-SIGN (CD209)
kines greatly improved our understanding of DC biology ( Fig. 11.2). Mono-
cytes treated with the cytokines granulocyte-macrophage colony-stimulating
factor (GM-CSF ) and interleukin (IL)-4 di¨erentiate into pathogen capturing
immature DC (Romani et al., 1994). Several factors, such as whole bacteria,
the microbial cell-wall component lipopolysaccharide ( LPS), cytokines, such as
IL-1 and tumor necrosis factor (TNF )-a, and CD40 ligation drive their di¨er-
entiation into mature DC ( Fig. 11.2).
Immature DC express a variety of molecules to mediate e½cient intake of
pathogens by endocytosis ( Table 11.2), including C-type lectins, such as DEC-
205 and the macrophage mannose receptor (Hart, 1997). These receptors bind
heavily glycosylated antigens via their C-type lectin domains such as those
commonly found on the surface of pathogens ( Drickamer, 1995), and have a
high turnover at the cell surface for e½cient internalization of bound antigen.
Immature DC contain specialized MHC class II-rich compartments, where
processed antigen is e½ciently loaded as peptides onto MHC class II molecules.
During maturation of DC, the stable complexes of these MHC class II-rich
compartments are discharged at the surface, where they remain for several days
enabling screening by CD4
T cells. Recognition of these complexes by T cells
and their subsequent activation requires the formation of a specialized junction
between these cells, the so-called immunological synapse, that is generated by
carefully orchestrated recruitment of speci®c adhesion receptors into the con-
tact site to strengthen DC±T-cell contact (Geijtenbeek et al., 2000b; Grakoui et
al., 1999; Monks et al., 1998). We have recently demonstrated that DC use the
DC-speci®c ICAM-3- and HIV-1-receptor DC-SIGN (CD209) to provide the
initial contact by interacting with ICAM-3 on the naive T cell. This interaction
provides positional stability and facilitates engagement of the T-cell receptor
(TCR) with peptide-MHC class II complexes. TCR-triggering initiates strong
adhesive LFA-1 (CD11a)-mediated interactions with ICAM-1 (CD54) on DC,
