Questions: Dendritic Cells and Professional Antigen-Presenting Cells

Question 1

A dendritic cell in peripheral tissue takes up antigen from a dying cell, but no pathogen-associated molecular patterns (PAMPs) or TLR signals are present. What is the most likely immunological outcome?

• A. The DC migrates to the lymph node and activates naive T cells, because antigen uptake is the trigger for migration
• B. The DC presents antigen but cannot activate T cells due to low costimulatory molecule expression, potentially inducing T cell tolerance instead
• C. The DC activates T cells via MHC class I only, since class II requires TLR signaling to load
• D. The DC undergoes apoptosis because antigen uptake without infection signals the cell to self-destruct

Answer: (B)

Immature DCs are efficient antigen capturers but poor T cell activators. Without TLR-mediated maturation signals, the DC does not upregulate costimulatory molecules (CD80/CD86) or increase surface MHC expression, and it does not acquire CCR7 to migrate to lymph nodes. An immature DC presenting antigen to a naive T cell without costimulation (signal 2) typically induces anergy or tolerance in the T cell rather than activation — a mechanism that normally prevents autoimmunity by tolerizing T cells against self-antigens presented in the absence of infection. The misconception in option A conflates antigen uptake with the maturation trigger.

Question 2

What is the key functional difference between an immature and a mature dendritic cell?

• A. Immature DCs present antigen on MHC class I; mature DCs present on MHC class II
• B. Immature DCs are found in lymph nodes; mature DCs patrol peripheral tissues
• C. Immature DCs excel at capturing antigen but lack costimulatory molecules; mature DCs lose phagocytic capacity but gain the ability to activate naive T cells
• D. Immature DCs activate CD8+ T cells; mature DCs activate CD4+ T cells

Answer: (C)

The two phases represent a functional switch: immature DCs in peripheral tissues are optimized for antigen capture (high phagocytic activity, macropinocytosis) but express low MHC and almost no B7 costimulatory molecules, so they cannot effectively activate T cells. TLR-mediated maturation reverses these priorities: phagocytic capacity decreases, MHC class I and II and costimulatory molecules (CD80, CD86) are dramatically upregulated, CCR7 is expressed to drive migration to lymph nodes, and the DC becomes capable of delivering both signal 1 (MHC-peptide) and signal 2 (costimulation) to naive T cells. Options A and D confuse class I/II with maturation state; option B reverses the tissue distribution.

Question 3

Because dendritic cells constitutively express MHC class II molecules at most stages of their development, they can effectively activate naive T cells at any point in their life cycle.

• T. True
• F. False

Answer: False

MHC class II expression alone is not sufficient for naive T cell activation. Immature DCs do express MHC class II, but at very low levels, and critically, they express almost no costimulatory molecules (B7/CD80/CD86). Naive T cell activation requires two signals: signal 1 (MHC-peptide binding the TCR) and signal 2 (costimulatory molecule binding CD28 on the T cell). Without signal 2, the T cell receiving signal 1 alone is typically driven into anergy or tolerance. Only after TLR-mediated maturation do DCs express sufficient MHC and costimulatory molecules to reliably activate naive T cells.

Question 4

Dendritic cells can cross-present exogenous antigens on MHC class I molecules, allowing them to activate CD8+ cytotoxic T cells against pathogens that have not directly infected the dendritic cell itself.

• T. True
• F. False

Answer: True

Cross-presentation is a specialized capability of dendritic cells (and some macrophages) that routes exogenously acquired antigen — taken up from infected or dying cells — into the MHC class I presentation pathway, which normally presents only endogenous (intracellular) peptides. This is immunologically critical: viruses and tumors that avoid infecting dendritic cells would otherwise escape CD8+ T cell recognition. Cross-presentation allows DCs to survey the entire tissue environment and initiate cytotoxic T cell responses against any cell type that is infected or transformed, making DCs indispensable for antiviral and antitumor immunity.

Question 5

Why is it not sufficient for a dendritic cell to simply display antigen on MHC molecules to activate a naive T cell? What additional signal is required, and why does this requirement matter biologically?

Model answer: T cell activation requires two signals: signal 1 is the MHC-peptide complex binding the T cell receptor, and signal 2 is costimulation via B7 molecules (CD80/CD86) on the APC binding CD28 on the T cell. Without signal 2, signal 1 alone typically induces T cell anergy or tolerance rather than activation. This two-signal requirement is biologically critical because it prevents inappropriate immune responses against self-antigens: immature DCs in tissues routinely present self-peptides on MHC, but without infection-triggered costimulatory upregulation, self-reactive T cells are tolerized rather than activated. The costimulation requirement thus serves as a gating mechanism ensuring that T cell responses are mounted only when genuine infection signals (PAMPs detected by TLRs) are present.

The two-signal model explains both normal immunity and autoimmune risk. In infection, PAMPs trigger DC maturation, costimulatory upregulation, and T cell activation — a productive response. In steady state, self-antigens are presented without costimulation, tolerizing autoreactive T cells. When this gate fails — for example if self-antigens are presented during inflammatory conditions that aberrantly upregulate costimulatory molecules — autoimmunity can result. Therapies that block costimulatory pathways (like CTLA-4-Ig) exploit this biology to treat autoimmune diseases and prevent transplant rejection.