“Meet Ups” between T Cells and Professional Antigen Presenting Cells in Lymph Nodes

Mature DC and Naive T Cell Interactions

When dendritic cells (DCs) carrying antigen migrate to the T cell area of lymph nodes, they interact with naive T cells that express cognate T cell receptors (TCRs) specific to the presented antigen. These interactions involve three key signals, known as “signal 1,” “signal 2,” and “signal 3,” which are crucial for the activation and differentiation of naive T cells.

1. Signal 1: Antigen Recognition by TCR-MHC Interaction:
   • Signal 1 is initiated when the TCR on the surface of a naive T cell recognizes antigenic peptides presented by major histocompatibility complex (MHC) molecules on the surface of the dendritic cell.
   • This interaction between the TCR and the antigen-MHC complex provides the primary signal for T cell activation. It triggers intracellular signaling pathways within the T cell, leading to the activation of transcription factors and the expression of early activation genes.
2. Signal 2: Co-stimulatory Signal:
   • Signal 2 is provided by co-stimulatory molecules expressed on the surface of the dendritic cell interacting with their corresponding receptors on the surface of the T cell.
   • One of the most important co-stimulatory interactions is between CD80/CD86 molecules on the dendritic cell and CD28 receptor on the T cell. This interaction enhances T cell activation and proliferation.
   • Without adequate co-stimulation (signal 2), T cell activation may be aborted, leading to T cell anergy or tolerance.
3. Signal 3: T Cell Polarizing Cytokines:
   • Signal 3 involves the production of polarizing cytokines by the dendritic cell, which influence the differentiation and functional specialization of activated T cells.
   • Dendritic cells produce various cytokines depending on the nature of the antigen encountered and the microenvironment. These cytokines can skew T cell differentiation towards different effector phenotypes, such as Th1, Th2, Th17, or Treg cells.
   • For example, interleukin-12 (IL-12) promotes differentiation into Th1 cells, which are important for cellular immunity against intracellular pathogens, while interleukin-4 (IL-4) promotes differentiation into Th2 cells, which are involved in humoral immunity and defense against extracellular parasites.
   • The cytokines produced by the dendritic cell provide crucial instructions to the activated T cells, shaping their functional properties and directing the type of immune response generated against the antigen.

In summary, the interactions between dendritic cells and naive T cells involve multiple signals that collectively orchestrate T cell activation, proliferation, and differentiation into effector T cell subsets. These signals ensure appropriate and tailored immune responses against encountered antigens.

Antigen-Experienced T Cell and Antigen-Experienced B Cell Interactions

When an activated T cell migrates to the boundary between the T-cell area and the B-cell area in the lymph node to interact with a B cell, the interaction between the T cell and the B cell involves several key signaling events, often referred to as signals 1, 2, and 3.

1. Signal 1 – Antigen Recognition: Signal 1 involves the recognition of the antigen presented by the B cell to the T cell. The T cell receptor (TCR) on the surface of the activated T cell interacts with the peptide antigen-MHC complex presented by the B cell. This interaction provides the primary signal that activates the T cell. If the antigen presented by the B cell matches the specificity of the TCR on the T cell, it triggers a cascade of intracellular signaling events leading to T cell activation.
2. Signal 2 – Co-stimulation: Signal 2 involves co-stimulatory signals that further activate the T cell and promote its proliferation and differentiation. One of the key co-stimulatory molecules involved in this interaction is CD40L, which is expressed on the surface of the T cell. CD40L interacts with CD40 expressed on the surface of the B cell. This interaction provides the necessary co-stimulatory signal for B cell activation and helps prevent inappropriate activation of B cells in the absence of danger signals.
3. Signal 3 – Cytokine Signaling: Signal 3 involves cytokine signaling via the production of cytokines by both the B cell and the T cell. IL-2 expression is important for cell survival and proliferation. The other cytokines produced and received by this interaction will depend on the PAMP recognized by the dendritic cell that activated the T cell and the PAMPs recognized by the B cell.

In summary, the interaction between the T cell and the B cell at the boundary between the T-cell area and the B-cell area of the lymph node involves antigen recognition (signal 1), co-stimulation (signal 2), and cytokine signaling (signal 3). These signals collectively orchestrate the activation, proliferation, and differentiation of both T cells and B cells, leading to the generation of an effective immune response against the encountered antigen.

Next Topic: Help Is on the Way: Recruitment of Helper T Cells to Peripheral Tissues

Source: ChatGPT response prompted and edited by Joel Graff.

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