Meeting in the T-zone
For antigen presentation to be successful, the participants of the process must converge in a strictly defined morphological region of the lymph node — the T-zone.
Cells reach this area via different routes:
- Dendritic cells (DCs) migrate from the body's barrier tissues along with the lymph flow. During this migration, the immature dendritic cell undergoes transformation and becomes mature.
- T-lymphocytes are in a state of continuous recirculation and enter the lymph node along with the blood flow, passing through the hilum of the organ.
It is precisely the convergence of mature DCs and recirculating T lymphocytes within the T-zone that creates the critical conditions for the subsequent formation of the immune synapse.
Molecular mechanism of directed migration
The convergence of cells of different origins in one location is not accidental; it is strictly controlled by a unified chemokine mechanism.
The key element is the chemokine receptor CCR7, which is expressed on the surface of both mature dendritic cells and T lymphocytes. This receptor is tuned to recognize specific ligands — the chemokines CCL19 and CCL21.
The sources of these chemoattractant molecules (chemokines) in the lymph node are high endothelial venule cells and stromal cells of the T-zone itself. In addition, chemokines are secreted by interdigitating (dendritic) cells localized here. Moving along the concentration gradient of these substances, T lymphocytes unerringly find their way to the target zone.
Extravasation: how T cells leave the bloodstream
To accumulate in a regional lymph node, a T cell must exit the bloodstream into the tissue. This process is called extravasation and occurs through the high endothelium of postcapillary venules.
To successfully cross the endothelial barrier, a T lymphocyte utilizes two main molecules on its membrane:
- L-selectin (CD62L) — acts as a homing receptor, providing initial tethering.
- CCR7 receptor — responds to the chemokine CCL21, which is secreted by the endothelial cells themselves.
Immediately after completing extravasation, the T cell continues its movement directly into the T-zone, guided by the gradient of CCL19 and CCL21 chemokines.
Capture of T-lymphocyte clones
There is an initial deficiency of antigen-specific T cells of a particular clone in the body. This problem is solved through the mechanism of recruitment (capture) during continuous recirculation.
Upon reaching the T-zone, T lymphocytes come into close contact with interdigitating cells, interacting with them via adhesion molecules and membrane receptors. Due to continuous circulation, any T cell will sooner or later pass through a lymph node containing the delivered antigen.
If high affinity is detected between the T-cell receptor (TCR) and the MHC–peptide complex on the dendritic cell, a stable contact zone is formed — the immune synapse. As a result, virtually all T lymphocytes of the required clone are retained in this regional node. Consequently, the efferent lymph becomes entirely depleted of T cells of this specific clone, whereas they are present in the afferent lymph.
Subsequent fate of T cells and experimental evidence
The fate of a lymphocyte directly depends on the outcome of recognition:
- If the specific antigen is absent: The T cell is not retained in the node, leaves it with the efferent lymph, and enters a new recirculation cycle.
- If the antigen is recognized: The cell's behavior changes dramatically, and its activation cascade is triggered.
The significance of the capture process has been proven experimentally. If an antigen combined with a stimulator (adjuvant) is injected into a laboratory mouse, and a few hours later this regional lymph node is surgically removed, the animal completely loses the ability to mount an immune response to this antigen. The reason is that all T cells specific to this antigen have already been "captured" and removed from the body along with the node.
Briefly: answers to topical questions
Which adhesion molecules mediate contact between the T lymphocyte and the dendritic cell in the immune synapse?
Contact between the T lymphocyte and the dendritic cell in the immune synapse is mediated by primary and secondary adhesion molecule complexes.
- $\beta_2$-integrin LFA-1 (LFA-1) — located on the T helper cell and binds to the ICAM-1 receptor on the dendritic cell.
- CD2 molecule (CD2) — located on the T helper cell and interacts with CD58 / LFA-3 molecules on the dendritic cell.
During synapse maturation, these adhesion molecules are displaced to the periphery of the contact zone, leaving the central part to molecules responsible for specific antigen recognition.
What signals are necessary for the full activation of a T lymphocyte after antigen recognition?
For the full activation of a T lymphocyte following antigen recognition, a second signal providing obligatory co-stimulation is required.
- First signal — recognition of the antigenic peptide presented within an MHC-I or MHC-II molecule by the cellular receptor TCR.
- Second signal — interaction of the CD28 receptor on the surface of the T lymphocyte with co-stimulatory molecules CD80 or CD86 (B7) on the antigen-presenting cell.
The combination of these two signals leads to full T-cell activation, triggering the expression of new molecules and the secretion of cytokines.
To remember the key migration molecules, use the rule: the CCR7 receptor helps T cells and DCs gather together in the T-zone by responding to chemokines 19 and 21.
Class and exam questions
What happens to a T lymphocyte if it does not find its antigen in the lymph node?
In this case, the T lymphocyte does not linger in the lymph node tissue for long. It leaves the node via the efferent lymph and enters the next cycle of systemic recirculation.
Why is the immune synapse necessary?
An immune synapse is a specialized supramolecular structure that forms upon antigen recognition. It is necessary to overcome the shortage of MHC molecules with specific peptides and ensure successful antigen presentation.
Why does the efferent lymph become depleted of specific T-cell clones?
Upon recognizing a specific antigen within the node, T cells of the required clone form an immune synapse with dendritic cells and are firmly retained in the T-zone for activation. Therefore, they cease to exit the node via the efferent lymph.
What else to study on this topic
- The transformation process of an immature dendritic cell into a mature one during migration.
- Detailed structure and functions of the immune synapse.
- Behavioral changes and stages of T-lymphocyte activation after antigen recognition.
- The role of adhesion molecules in intercellular interactions within the T-zone.
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