Antigen-Presenting Cells and Antigen Processing
Why T cells cannot manage on their own ★★★
Both T and B cells recognise antigen specifically, through TCR and BCR — but they do it by completely different mechanisms, and the difference is the reason this unit exists. B cells recognise native antigen: the BCR touches the intact molecule. T cells recognise only antigen that has been processed and presented by an APC.
Cell populations that can capture and process antigens, and present them to T lymphocytes.Section I, 2019
A T cell cannot read a bacterium. It can only read a short peptide sitting in an MHC groove — so something has to convert one into the other. That conversion is processing: take the antigen in, cut it up, load a fragment onto MHC, put it back on the surface.
So the APC is a translator standing between the world of whole pathogens and the world of peptide–MHC that T cells inhabit. Everything else in this unit is how the translation is done — and the answer turns out to depend entirely on where the antigen came from.
- Define APC. → Cell populations that capture and process antigens and present them to T lymphocytes
- How does B-cell recognition differ from T-cell recognition? → B cells see native antigen; T cells see only processed antigen presented on MHC
Professional and non-professional APCs ★★★
| Members | |
|---|---|
| Professional APCs | Dendritic cells · Macrophages · B cells |
| Non-professional APCs | Fibroblasts (skin) · thymic epithelial cells · glial cells (brain) · thyroid epithelial cells · pancreatic β cells · vascular endothelial cells |
What makes an APC 'professional' is the ability to express MHC class II — which is why the professional list matches the class II distribution from Unit 10 exactly. Non-professional APCs can be induced to express class II under inflammatory conditions, but they do not do so constitutively, and they lack the co-stimulatory molecules needed to activate a naïve T cell.
- Name the three professional APCs. → Dendritic cells, macrophages, B cells
- What defines a professional APC? → Constitutive MHC class II expression
- Give three non-professional APCs. → Fibroblasts, thymic and thyroid epithelial cells, glial cells, pancreatic β cells, vascular endothelium
Dendritic cells ★★★
Of the three professional APCs, one is different in kind rather than degree. Macrophages and B cells present antigen as a sideline — their main jobs are phagocytosis and antibody production. The dendritic cell does nothing else. It exists to collect antigen and show it to T cells, and that single-mindedness is why it is the only cell that can start an immune response from nothing.
DCs were found by Steinman in 1973 and named for their branched, dendrite-like shape; Steinman shared the 2011 Nobel Prize for the discovery — the same prize that recognised Beutler and Hoffmann for PRRs in Unit 9. All three discoveries are about how the innate system starts the adaptive one.
| Classification | Types |
|---|---|
| By derivation | Myeloid DC (DC1) — from myeloid stem cell Lymphoid DC (DC2) — from lymphoid stem cell |
| By function | Immature DC and Mature DC — see §4 |
The phrase “primary immune response” is the key. A primary response means activating a naïve T cell — and the dendritic cell is the only APC that can. Macrophages and B cells present very effectively to T cells that have already been activated. Neutrophils are not APCs at all.
- Who discovered dendritic cells, and when? → Steinman, 1973 (Nobel Prize 2011)
- How are DCs classified by derivation? → Myeloid DC (DC1) and lymphoid DC (DC2)
- Which APC can activate a naïve T cell? → The dendritic cell only — hence MCQ Q8
- Why is the DC called the initiator of the immune response? → It alone can start a primary response
Immature versus mature DC ★★★
| Immature DC | Mature DC | |
|---|---|---|
| MHC I / II | +++ | ++++ |
| Co-stimulatory molecules (B7, ICAM-1, LFA-3) | Low level | High level |
| Antigen uptake | ++++ | + |
| Antigen processing | ++++ | + |
| Antigen presentation | + | ++++ |
| Cytokine secretion | Not clear | IL-12, IL-18, IFN-γ, chemokines |
| Location | Peripheral tissue | Secondary lymphoid organs |
A. Strongly internalize antigens but have no presentation ability B. Low levels of class II MHC and B7 C. Strongly present antigens but can't uptake antigens D. Reside in peripheral tissue
A DC cannot be good at both jobs at once, and the reason is geographical. To collect antigen it must sit in peripheral tissue where pathogens arrive. To present it must be in a lymph node where naïve T cells circulate. It cannot be in both places, so it does one and then the other.
Encountering a pathogen triggers the switch: the DC stops eating, migrates to the draining lymph node, and converts everything it already swallowed into surface peptide–MHC with high B7. It stops sampling and starts reporting.
And the design is safe as well as efficient. Because it stops taking up antigen on the way, what it presents in the node is a snapshot of the tissue at the moment of danger — not a mixture contaminated by whatever it passed through en route.
- Which DC takes up antigen well? → The immature DC (++++)
- Which presents antigen well? → The mature DC (++++)
- What happens to co-stimulatory molecules on maturation? → They rise from low to high
- Where does each reside? → Immature in peripheral tissue; mature in secondary lymphoid organs
- Which cytokines does the mature DC secrete? → IL-12, IL-18, IFN-γ and chemokines
The three professional APCs compared ★★
| Dendritic cell | Macrophage | B cell | |
|---|---|---|---|
| Antigen uptake | Pinocytosis +++ | Phagocytosis, pinocytosis, receptor-mediated endocytosis +++ | Ig-mediated ++++ |
| MHC expression | Constitutive ++++ | Inducible — by bacteria and cytokines | Constitutive +++ |
| Co-stimulatory molecules (B7) | Constitutive ++++ | Inducible, − to +++ | Inducible, − to +++ |
| Antigens presented | Peptides, viral antigens, allergens | Particulate; intracellular and extracellular pathogens | Soluble antigens, toxins, viruses |
| Location | Widespread | Widespread | Lymphoid tissue, peripheral blood |
Two rows explain everything else. The DC alone expresses MHC and B7 constitutively — it is permanently equipped to give both signals, which is exactly why it and it alone can activate a naïve T cell (MCQ Q8). Macrophages and B cells must be induced first, and something has to have activated them already.
And the uptake row explains the division of labour: the B cell's Ig-mediated uptake is ++++, the best of the three, because the BCR concentrates its own specific antigen — which is why B cells specialise in soluble antigens and toxins that macrophages cannot capture efficiently.
- Which APC expresses MHC and B7 constitutively? → The dendritic cell
- How does a B cell take up antigen? → Ig-mediated, via the BCR — the most efficient of the three
- Which antigens does the B cell specialise in? → Soluble antigens, toxins, viruses
- Which APC has inducible MHC expression? → The macrophage
The class I pathway — endogenous antigen ★★★
Now the actual translation. There are two processing pathways, and which one an antigen enters is decided by one thing only: which compartment of the cell it is sitting in. Protein floating in the cytosol goes one way; protein inside a membrane vesicle goes the other. Nothing about the antigen's identity matters — a viral protein and a self protein in the cytosol are handled identically.
The class I pathway handles the cytosol. Its problem is a physical one: MHC class I is assembled inside the endoplasmic reticulum, but the peptides it needs are out in the cytosol, on the wrong side of a membrane. The pathway is essentially a solution to that geography — chop the protein up outside, then pump the fragments in.
Antigen that comes from inside the cell — viral proteins, tumour proteins — i.e. protein synthesised within the host cell itself.
- Antigen proteins are synthesised by the target cell — for example a virus forcing the cell to make viral protein.
- Proteasomes cleave them into peptides. The proteasome is a large cylindrical particle with a central channel, which cleaves peptide bonds.
- Peptides are transported from the cytosol into the rough endoplasmic reticulum — by TAP1/TAP2, themselves MHC-encoded (Unit 10).
- Peptides assemble with class I MHC in the ER.
- The peptide–class I complex is expressed on the cell surface and presented to CD8⁺ T cells.
Endogenous → proteasome → TAP → class I → CD8⁺ CTL. Every nucleated cell can do this, because every nucleated cell carries class I.
- What is an endogenous antigen? → One made inside the cell — viral or tumour protein
- What cleaves it? → The proteasome
- How does the peptide reach the ER? → Via the TAP transporter
- Which MHC class does it load onto, and which T cell sees it? → Class I, seen by CD8⁺ T cells
The class II pathway — exogenous antigen ★★★
The class II pathway has the opposite geography and therefore a much simpler solution. Antigen taken in by endocytosis is already inside a vesicle, and MHC class II travels out to meet it in that same vesicular system. No transporter is needed and no membrane has to be crossed — the two simply arrive in the same compartment and the peptide is loaded there.
Antigen that comes from outside the cell — bacteria, other cells, protein — and is taken up by endocytosis.
- Exogenous antigen is taken up by endocytosis into the APC.
- It is degraded in the endosome/lysosome into peptide fragments.
- Peptides combine with class II MHC molecules.
- The peptide–class II complex is expressed on the surface and presented to CD4⁺ helper T cells.
Exogenous → endocytosis → lysosome → class II → CD4⁺ helper T cell. Only professional APCs can do this, because only they carry class II.
Put the pathways side by side and the logic is unmistakable. Each answers a different question, and the answer determines what should happen next.
Class I asks: is this cell itself compromised? The antigen came from the cytosol, so the cell is making it — it is infected or transformed. The correct response is to kill this cell, so the peptide goes to a CD8⁺ CTL.
Class II asks: is there something out there? The antigen was swallowed from outside, so the APC itself is healthy — it is a scout reporting. Killing it would be senseless; the correct response is to organise a response, so the peptide goes to a CD4⁺ helper.
The compartment the antigen came from determines the MHC class, which determines the T cell, which determines the outcome. That is the entire architecture of cell-mediated immunity in one sentence.
| Class I pathway | Class II pathway | |
|---|---|---|
| Antigen source | Endogenous — cytosolic | Exogenous — endocytosed |
| Examples | Viral proteins, tumour proteins | Bacteria, other cells, soluble protein |
| Degraded by | Proteasome | Endosome / lysosome |
| Transport | TAP, into the ER | Vesicular trafficking |
| Loaded onto | MHC class I | MHC class II |
| Presented to | CD8⁺ T cells | CD4⁺ T cells |
| Which cells can do it | All nucleated cells | Professional APCs only |
| Outcome | Kill the presenting cell | Organise a response |
- What is an exogenous antigen? → One taken up from outside — bacteria, cells, protein
- Where is it degraded? → In the endosome/lysosome
- Which MHC class, and which T cell? → Class II, presented to CD4⁺ helper T cells
- Why does endogenous antigen lead to killing? → The cell is making it, so the cell itself is compromised
- Which cells can use the class II pathway? → Only professional APCs — they alone have class II
Revision layer
The exam map for this unit
| Section | Item | From |
|---|---|---|
| I. Definitions | APCs — set 2019 | §1 |
| II. Fill in blanks | Professional APCs — macrophage, DC, B cell | §2 |
| III. MCQ Q8 | DC is the most powerful APC, elicits the primary response | §3 |
| III. MCQ Q14 | Mature DC presents strongly but cannot take up antigen | §4 |
The whole unit on one screen
| Question | Answer |
|---|---|
| Define APC | Cells that capture and process antigen and present it to T lymphocytes |
| Professional APCs? | DC · macrophage · B cell |
| What makes them professional? | Constitutive MHC class II expression |
| Most powerful APC? | DC — the only one that activates naïve T cells |
| Immature DC is good at? | Antigen uptake and processing (++++) |
| Mature DC is good at? | Antigen presentation (++++) |
| Which APC uses Ig-mediated uptake? | The B cell — best uptake of the three |
| Endogenous antigen route? | Proteasome → TAP → class I → CD8⁺ |
| Exogenous antigen route? | Endocytosis → lysosome → class II → CD4⁺ |
| Which cells can present on class I? | All nucleated cells |
| Which on class II? | Professional APCs only |
eNdogenous — made iNside — class I — CD8.
eXogenous — from outside, eXternal — class II — CD4.
Then apply Unit 10's arithmetic to check yourself: class I × CD8 = 8, class II × CD4 = 8.
- Define APC. → Cells that capture and process antigen and present it to T lymphocytes
- Name the three professional APCs. → DC, macrophage, B cell
- Which is most powerful, and why? → DC — it alone activates naïve T cells and initiates the primary response
- Immature vs mature DC in one line? → Immature takes up and processes; mature presents
- Trace the class I pathway. → Endogenous protein → proteasome → TAP → ER → class I → surface → CD8⁺
- Trace the class II pathway. → Exogenous antigen → endocytosis → lysosomal degradation → class II → surface → CD4⁺
- Why does the compartment determine the outcome? → Cytosolic antigen means the cell is compromised (kill it); external antigen means the APC is a scout (organise a response)