DCs have been identified as the most effective antigen presenting cells (APC). They have long dendritic processes and possess an exceptional capability to capture antigens (Ags), process and present antigenic peptide fragments, migrate to lymphoid organs, and induce primary immune responses of both CD8+ and CD4+ . They have been described as nature’s adjuvant, specialized antigen-presenting cells for initiating immunity. DCs provide three signals to T lymphocytes:

Mucosal DCs provide an important first line of defense by ingesting foreign invaders via both pincytosis and receptor-mediated endocytosis. While the receptor is recylced to the cell surface, the endocytic compartment that contains the internalized antigen fuses with a lysosome that contains hydrolytic enzymes, which degrade the antigen into oligopeptides. Next, an endosome containing DC  (MHC II) molecule fuses with the compartment containing the peptides. Each MHC II receptor binds a single peptide while being transported to the DC membrane, where MHC II is constitutively expressed. The MHC II-peptide receptor complex serves to initiate a signaling pathway for activation in CD4+ T cells vial interaction with the TCR. Also known as T-helper cells, these activated CD4+ T cells mobilize key players in the humoral and cell-mediated arms of the immune system and coordinate their activities via secretion of cytokines. The formation of a MHCII-peptide-TCR complex is specific: a large repertoire of TCRs with highly variable extracellular regions exist, since a TCR must recognize and bind both the MHCII molecule and the attached peptide.

The story of virally infected DCs involves an alternate endogenous processing pathway. Most viral proteins are produced in the cytosol, where a ubiquinating enzyme complex covalently links several small ubiquitin proteins to a lysine-amino group near the amino terminus of the viral protein. Ubiquitin-protein complexes are targeted for degradation by a cylindrical protease complex called a proteasome, and eukaryotic cells use this general mechanism to regulate all protein levels, especially those of abnormal or foreign proteins. The viral peptides produced are transported by a transporter associated with antigen processing (TAP) protein into the rough endoplasmic reticulum, where each peptide is bound by a DC  molecule. MHC I is similar to MHC II in that it also is constitutively expressed on the DC membrane. However unlike MHC II, the MHC I-peptide receptor complex is recognized by CD8+ T cells via their TCRs. Activated CD8+T cells differentiate into cytotoxic T lymphocytes primed to destroy other infected cells.

An exception to this pathway may occur following synthesis of viral envelope proteins, which are translocated into the ER and destined for the cell surface in endocytic compartments after passing through the Golgi. First lysosomes and then MHCII-containing endosomes fuse with these compartments. MHCII molecules bind peptides from these proteins and these complexes are presented on the CD surface to T-helper cell recognition. Alternatively, the envelope proteins may reach the cell membrane, and fusion with MHCII containg endosomes may occur follwwing endocytosis of these envelope proteins form the cell surface.

DCs constitutively express high levels of class I and II MHC molecules as well as high levels of B7-1 and B7-2. In contrast, all other  require activation for expression of co-stimulatory B7 molecules on their membranes. In response to inflammatory stimuli, such as LPS, DC precursors migrate to T cell zones of lymph nodes and mature into effective APCs by ceasing endocytosis, stabilizing expression of class II-peptide complexes, and increasing expression of B7.1 or B7.2. 

The communication between DCs and T cells seems to be a dialogue rather than a monologue in which the DCs respond to T cells as well. CD40 and the newly described TRANCE/RANK receptor on DCs are ligated by the TNF family of proteins expressed on activated and memory T cells: this leads to increased DC survival and in the case of CD40, upregulation of CD80 and CD86, secretion of and release of chemokines such as IL-8, MIP-1 alpha and beta.

Cytokine cocktails that polarize the merging T cell response toward either cytotoxicity or immune regulation through differentiation of TH1 (Il-2, IFN-y) or TH2 (IL-4, 5, 10) of TH- type secretion patterns. For instance, IL-12 is important to prime for TH1 type responses; anti-inflammatory molecules such as IL-12, TGF-B, PGE-2 and corticosteroids, inhibit IL-12 production and DC maturation and induce TH2-type or regulatory responses; Signal 3 is crucial in the interplay between innate and adaptive immunity.

Stages of activation:

T-cell priming by DCs occurs in 3 successive stages. (1) transient serial encounters (2) followed by stable contacts culminating in cytokine production by T cells (IL-2 and IFN-y) and then (3) high motility and rapid proliferation of T cells.