CCR7 and its ligands link innate immunity and adaptive immunity through their effects on interactions between T lymphocytes and dendritic cells.
During innate immune responses, phagocytes and soluble factors rather nonspecifically eliminate or neutralize pathogens.
By contrast, the adaptive immune responses generated by B cells and T cells have specificity and memory.
Adaptive immunity begins in lymphoid organs, where mature dendritic cells or macrophages present immunogenic peptides to naive or memory T cells. This encounter is governed with remarkable precision by two chemokines, CCL19 and CCL21, and their receptor, CCR7.
Once immature dendritic cells ingest antigen and become able to present antigen to T cells, they increase their display of CCR7.
These CCR7+ dendritic cells enter lymph nodes through the afferent lymph or the bloodstream, using vessel-bound CCL19 and CCL21 to sense their destination.
Naive or memory T cells enter through high endothelial venules, using the same receptors and cues. Once inside the lymph node, CCR7+ dendritic cells and T cells follow gradients of CCL19 and CCL21 in T-cell zones to find one another.
Given the low likelihood that any individual dendritic cell will present the "right" immunogenic peptide to a particular T cell, this process must be repeated continuously and with high efficiency to increase the probability that clones of antigen-specific T cells will be activated.
Mice lacking CCR7 (through targeted gene deletion) or that have insufficient CCL19 or CCL21 (through naturally occurring mutation) have structurally disorganized lymph-node T-cell zones and are deficient in T-cell–dependent immunity.
Another receptor–ligand pair, CXCR5 and CXCL13, establish and coordinate the B-cell zones of lymph nodes. After antigen binding, B cells up-regulate CCR7 and move to the boundaries between B-cell and T-cell zones to interact with helper T cells.
See also
CCRs
chemokines