DEVELOPMENTAL REGULATION OF MHC CLASS-II TRANSPORT IN MOUSE DENDRITICCELLS

Dendritic cells (DCs) have the unique capacity to initiate primary and secondary immune responses(1-3). They acquire antigens in peripheral tissues and migrate to lymphoid organs where they present processed pe ptides to T cells. DCs must therefore exist in distinct functional sta tes, an idea that is supported by observations that they downregulate endocytosis and upregulate surface molecules of the class II major his tocompatibility complex (MHC) upon maturation(4-7). Here we investigat e the features of DC maturation by reconstituting the terminal differe ntiation of mouse DCs in vitro and in situ. We find that early DCs, co rresponding to those found in peripheral tissues, exhibit a phenotype in which most class II molecules are intracellular and localized to ly sosomes. Upon maturation, these cells give rise to a new intermediate phenotype in which intracellular class II molecules are found in perip heral non-lysosomal vesicles, similar to the specialized CIIV populati on seen in B cells. The intermediate cells then differentiate into lat e DCs which express almost all of their class II molecules on the plas ma membrane. These variations in class II compartmentalization are acc ompanied by dramatic alterations in the intracellular transport of the ne iv class II molecules and in antigen presentation. We found that a lthough 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 pr operty crucial to their role in immune surveillance.