Dendritic cells (DCs) have the unique capacity to initiate primary and secondary immune
responses. They acquire antigens in peripheral tissues and migrate to lymphoid organs where
they present processed peptides to T cells. DCs must therefore exist in distinct functional
states, an idea that is supported by observations that they downregulate endocytosis and
upregulate surface molecules of the class II major histocompatibility complex (MHC) upon
maturation. Here the authors investigate the features of DC maturation by reconstituting the
terminal differentiation of mouse DCs in vitro and in situ. They find that early
DCs, corresponding to those found in peripheral tissues, exhibit a phenotype in which most
class II molecules are intracellular and localized to lysosomes. Upon maturation, these cells
give rise to a new intermediate phenotype in which intracellular class II molecules are found
in peripheral non-lysosomal vesicles, similar to the specialized CIIV population seen in B
cells. The intermediate cells then differentiate into late DCs which express almost all of their
class II molecules on the plasma membrane. These variations in class II compartmentalization
are accompanied by dramatic alterations in the intracellular transport of the new class II
molecules and in antigen presentation. They found that although early DCs could not present
antigen immediately after uptake, efficient presentation of the previously internalized antigen
occurred after maturation, 24--48 hours later. By regulating class II transport and
compartmentalization, DCs are able to delay antigen display, a property crucial to their role in
immune surveillance.
P Pierre, S J Turley, E Gatti, M Hull, J Meltzer, A Mirza, K Inaba, R M Steinman & I
Mellman
Developmental regulation of MHC class II transport in mouse dendritic cells (Letter to
Nature)
Nature 388, 787 (1996)
Nature © Macmillan Publishers Ltd. 1997
Registered No. 785998 England.