ABSTRACT

In general, the subset of antigen-presenting cells (APCs) that is uniquely well equipped for presenting antigen to T cells and is regarded as sentinels for inducing immune responses is the dendritic cell (DC) subpopulation (1,2). T cells recognize antigens presented by major histocompatibility complex (MHC) molecules expressed on the APCs, and the subsequent interactions determine the differentiation pathway for the T cell. APCs are made up of a heterogeneous family of cells that is able to process both exogenous and endogenous antigens into 10-20 amino acid peptides and load them on to MHC molecules, which then traffic to the membrane for subsequent recognition by the antigen-specific T-cell receptor (3,4). APCs may be further classified into professional APCs (bone-marrow-derived DCs), which are able of activating and inducing clonal expansion of both naïve and memory T cells and nonprofessional APCs (B lymphocytes, monocytes, macrophages, endothelial cells), which are able to stimulate memory T cells but are poorly equipped to stimulate naïve cells to differentiate into effector cells. Within the tissues, the DC phenotype is immature but is capable of maturation if presented with “danger” signals (5-7). The immature phenotype also matures in

response to signals from innate cells [natural killer (NK), NKT, γδ cells] (8). In return, the innate cell may become activated. Besides expression of co-receptors (CD80, CD86, Ox40 ligand, CD40), mature DCs exhibit decreased endocytosis of extracellular antigens, translocate the peptide-loaded MHC molecules into the plasma membrane, and display long-lasting peptide MHC complexes. Mature DCs also display increased membrane expression of chemokine receptor CCR7 (3), which responds to a gradient of chemokines released from the stromal cells residing in the T-cell areas of the secondary lymphoid organs (9).