Antigen Presenting

📋 Key Information Summary

📋

Antigen-presenting cells (APCs) process protein antigens into peptide fragments and display them on major histocompatibility complex (MHC) molecules for T-cell recognition — the essential first step in adaptive immunity.
Professional APCs comprise three principal cell types: dendritic cells (DCs), macrophages, and B cells, with DCs being the most potent naïve T-cell activators.
Two major antigen-processing pathways exist: the MHC class I (endogenous/cytosolic) pathway presents intracellular antigens to CD8⁺ T cells, while the MHC class II (exogenous/endosomal) pathway presents extracellular antigens to CD4⁺ T cells.
Cross-presentation allows certain DC subsets to load exogenous antigens onto MHC class I molecules, enabling CD8⁺ responses against viruses and tumours that do not directly infect APCs.
The MHC-peptide-TCR interaction provides two signals for T-cell activation: Signal 1 (antigen-specific) via TCR–pMHC engagement and Signal 2 (co-stimulation) via CD28–B7 or other co-stimulatory pairs.
Absence of Signal 2 following TCR engagement leads to T-cell anergy — a mechanism of peripheral tolerance exploited therapeutically with CTLA-4-Ig (abatacept).
Dendritic cell maturation status critically determines immune outcome: immature DCs promote tolerance, while mature DCs promote effector responses.
Clinical relevance spans vaccination (adjuvant design targets DC activation), transplant immunology (donor APC presentation drives rejection), autoimmune disease (aberrant self-antigen presentation), and immunodeficiency (defective APC function).
Antigen presentation defects underlie several primary immunodeficiencies, including MHC class II deficiency (bare lymphocyte syndrome type II) and MHC class I deficiency (TAP1/TAP2 deficiency).
Checkpoint inhibitors (anti-PD-1, anti-CTLA-4) work downstream of antigen presentation to reverse T-cell exhaustion, underscoring the clinical centrality of the APC–T-cell synapse.

Introduction & Australian Context

Antigen-presenting cells (APCs) are specialised immune cells that capture, process, and display peptide fragments on major histocompatibility complex (MHC) molecules to T lymphocytes, thereby initiating and directing adaptive immune responses. This process — antigen presentation — is the central event linking innate pathogen detection to antigen-specific T-cell activation, and it underpins protective immunity, immune tolerance, and immunopathology.

In Australian clinical practice, understanding antigen presentation is directly relevant to vaccination programmes (National Immunisation Programme), transplant medicine, oncology immunotherapy, autoimmune disease management, and the diagnosis of primary immunodeficiencies. Australia's multicultural population and the burden of chronic hepatitis B in Aboriginal and Torres Strait Islander communities highlight the importance of robust APC-mediated CD8⁺ T-cell responses for viral clearance.

This guideline provides a structured overview of professional APCs, antigen-processing pathways, the molecular basis of MHC–peptide–TCR interaction, and the requirements for T-cell activation, with emphasis on clinical applications in the Australian healthcare context.

Professional Antigen-Presenting Cells

Three cell types are classified as professional APCs because they constitutively express MHC class II molecules and provide co-stimulatory signals required for naïve T-cell activation. Non-professional APCs (e.g., epithelial cells, endothelial cells) may upregulate MHC class II under inflammatory conditions but lack the co-stimulatory capacity to prime naïve T cells.

Dendritic Cells

Dendritic cells (DCs) are the most potent professional APCs and are uniquely capable of activating naïve T cells. They are strategically positioned at body surfaces (skin, mucosae) and in lymphoid organs, forming a sentinel network for antigen capture.

DC Subset	Location	Key Markers	Primary Function
Conventional DC1 (cDC1)	Lymphoid and peripheral tissues	CD141 (BDCA-3), XCR1, CLEC9A	Cross-presentation to CD8⁺ T cells; IL-12 production; antiviral and antitumour immunity
Conventional DC2 (cDC2)	Lymphoid and peripheral tissues	CD1c (BDCA-1), CD11b	MHC class II presentation to CD4⁺ T cells; Th1, Th2, Th17 polarisation
Plasmacytoid DC (pDC)	Blood, lymphoid tissue	CD303 (BDCA-2), CD123	Massive type I interferon production; antiviral innate immunity; modest APC function
Langerhans cells	Epidermis	CD1a, Langerin (CD207), Birbeck granules	Skin antigen surveillance; capture antigens via extending dendrites
Monocyte-derived DC (moDC)	Inflammatory sites	CD14 (variable), CD11c, DC-SIGN	Recruited during inflammation; bridge innate and adaptive immunity

✅

Clinical pearl: DC maturation is the pivotal checkpoint. Immature DCs capture antigen efficiently but express low MHC class II and minimal co-stimulatory molecules — they promote T-cell tolerance. Upon activation by PAMPs/DAMPs via pattern-recognition receptors (TLRs, RLRs, CLRs), DCs upregulate MHC class II, CD80 (B7-1), CD86 (B7-2), and CD40, migrate to draining lymph nodes, and become potent T-cell activators. Vaccination adjuvants (e.g., AS01 in Shingrix®, aluminium salts in paediatric vaccines) function primarily by promoting DC maturation.

Macrophages

Macrophages are tissue-resident phagocytes derived from yolk-sac progenitors and circulating monocytes. While primarily effectors of innate immunity (phagocytosis, cytokine production), they serve as important APCs in the context of ongoing infection and inflammation.

Antigen uptake: Phagocytosis, macropinocytosis, receptor-mediated endocytosis (Fc receptors, complement receptors, mannose receptor)
MHC class II expression: Constitutive but upregulated by IFN-γ; macrophages are major APCs in granulomatous inflammation (e.g., tuberculosis, sarcoidosis)
Co-stimulation: Express CD80/CD86 upon activation; less potent than DCs at priming naïve T cells but effective at restimulating effector/memory T cells at sites of inflammation
Cytokine milieu: M1 macrophages (classically activated) produce IL-12 and promote Th1 responses; M2 macrophages (alternatively activated) produce IL-10 and promote Th2/regulatory responses
Clinical relevance: In tuberculosis, infected macrophages present mycobacterial antigens to CD4⁺ T cells; granuloma formation depends on macrophage–T-cell interaction. In Australia, TB remains relevant in Aboriginal and Torres Strait Islander communities and among migrants from endemic regions.

B Cells

B lymphocytes function as specialised APCs that capture antigen via their B-cell receptor (BCR/surface immunoglobulin), providing exquisite antigen specificity even at very low antigen concentrations.

Antigen capture: BCR-mediated endocytosis — the BCR binds native (unprocessed) antigen with high specificity, internalises it, and processes it for MHC class II presentation
MHC class II expression: Constitutive; upregulated by CD40 ligand (CD154) on activated T cells — the basis of T–B cooperation
Co-stimulation: Express CD80/CD86 upon activation; also present antigen to CD4⁺ follicular helper T cells (Tfh) in germinal centres
Functional significance: B-cell antigen presentation to Tfh cells is essential for germinal centre reactions, affinity maturation, class-switch recombination, and long-lived plasma cell/memory B-cell generation
Clinical relevance: Rituximab (anti-CD20) depletes B cells and reduces B-cell antigen presentation, contributing to its efficacy in B-cell lymphomas and autoimmune diseases (e.g., ANCA-associated vasculitis, rheumatoid arthritis)

⚠️

Key distinction: While all three professional APCs express MHC class II, only dendritic cells can efficiently prime naïve T cells. Macrophages and B cells preferentially restimulate previously activated (effector/memory) T cells. This hierarchy is clinically important: DC-targeted vaccines elicit broader primary responses, while B-cell depletion affects established memory responses.

Antigen Processing Pathways

Antigen processing refers to the proteolytic degradation of proteins into peptide fragments (typically 8–25 amino acids) that are loaded onto MHC molecules within specific intracellular compartments. The two classical pathways are defined by the source of antigen and the MHC class to which peptides are presented.

MHC Class I Pathway (Endogenous/Cytosolic Pathway)

This pathway processes intracellular proteins — including viral proteins synthesised within infected cells and mutant proteins in tumour cells — for presentation to CD8⁺ cytotoxic T lymphocytes.

1

Proteasomal Degradation

Cytosolic proteins are ubiquitinated and degraded by the proteasome (immunoproteasome in IFN-γ-stimulated cells) into peptide fragments of 8–16 amino acids.

2

TAP Transport

Peptides are translocated from the cytosol into the endoplasmic reticulum (ER) lumen by the transporter associated with antigen processing (TAP1/TAP2 heterodimer).

3

Peptide Loading Complex

Within the ER, peptides are loaded onto nascent MHC class I molecules (HLA-A, HLA-B, HLA-C) with the assistance of the peptide-loading complex (tapasin, ERp57, calreticulin).

4

Surface Expression

Stable pMHC class I complexes are transported via the Golgi to the cell surface for recognition by CD8⁺ T cells. Nucleated cells constitutively express MHC class I.

MHC Class II Pathway (Exogenous/Endosomal Pathway)

This pathway processes extracellular antigens that have been internalised by professional APCs — via phagocytosis, receptor-mediated endocytosis, or macropinocytosis — for presentation to CD4⁺ T helper cells.

1

Antigen Uptake

Extracellular antigens are internalised into endosomes/phagosomes via phagocytosis, pinocytosis, or receptor-mediated endocytosis (Fc receptors, mannose receptor, DEC-205).

2

Endosomal Proteolysis

Progressive acidification activates proteases (cathepsins B, D, L, S) that degrade proteins into peptides of 13–25 amino acids within late endosomes/MIIC.

3

CLIP Removal & Peptide Loading

The invariant chain (Ii/CD74) chaperones MHC class II to the MIIC, where cathepsin S degrades Ii leaving the CLIP fragment. HLA-DM catalyses CLIP exchange for antigenic peptide.

4

Surface Expression

Stable pMHC class II complexes traffic to the cell surface for CD4⁺ T-cell recognition. Expression is restricted to professional APCs (DCs, macrophages, B cells) and activated epithelial/endothelial cells.

Cross-Presentation

Cross-presentation is a specialised pathway by which certain DC subsets (primarily cDC1) load exogenous antigens onto MHC class I molecules, enabling CD8⁺ cytotoxic T-cell responses against pathogens or tumour cells that do not directly infect APCs.

Cytosolic pathway: Exogenous antigens escape from endosomes into the cytosol → proteasomal degradation → TAP-dependent ER loading onto MHC class I
Vacuolar pathway: Antigens are processed by endosomal/lysosomal proteases and loaded onto MHC class I within the endosome itself
Clinical significance: Cross-presentation is essential for antitumour immunity, antiviral CD8⁺ responses against non-APC-tropic viruses, and the efficacy of many cancer vaccines. Therapeutic strategies to enhance cross-presentation are under active investigation in Australian immunotherapy trials.

ℹ️

Autophagy and MHC class II: During starvation or intracellular infection, autophagy delivers cytosolic antigens to autophagosomes that fuse with MHC class II loading compartments. This enables presentation of endogenous antigens on MHC class II to CD4⁺ T cells — a mechanism relevant to immune responses against intracellular bacteria (e.g., Mycobacterium tuberculosis) and to autoimmunity.

MHC-Peptide-TCR Interaction

The physical interaction between the peptide–MHC complex on the APC surface and the T-cell receptor (TCR) on the T lymphocyte is the molecular foundation of adaptive immune recognition. This interaction determines antigen specificity, MHC restriction, and the activation threshold for T-cell responses.

MHC Molecules

Feature	MHC Class I	MHC Class II
Gene loci (human)	HLA-A, HLA-B, HLA-C (chromosome 6p21)	HLA-DR, HLA-DQ, HLA-DP (chromosome 6p21)
Protein structure	α chain (α1, α2, α3 domains) + β₂-microglobulin	α chain (α1, α2) + β chain (β1, β2)
Peptide-binding groove	Closed ends — accommodates 8–11 mer peptides	Open ends — accommodates 13–25+ mer peptides
Expression	All nucleated cells; platelets	Professional APCs (constitutive); inducible on others
T-cell partner	CD8⁺ cytotoxic T lymphocytes	CD4⁺ T helper cells
Accessory molecule	CD8 binds α3 domain — stabilises interaction	CD4 binds β2 domain — stabilises interaction

TCR Structure and Diversity

The TCR is a heterodimer of α and β chains (in αβ T cells) or γ and δ chains (in γδ T cells), each comprising variable (V) and constant (C) regions
TCR diversity is generated by somatic V(D)J recombination during thymic development, yielding an estimated repertoire of >10¹⁵ unique TCRs
The complementarity-determining region 3 (CDR3) loops of both α and β chains make direct contact with the peptide, providing antigen specificity
CDR1 and CDR2 loops (germline-encoded) primarily contact the MHC helices, providing MHC restriction

The Immunological Synapse

Upon TCR engagement with pMHC, a specialised junction — the immunological synapse — forms between the T cell and the APC. This supramolecular activation cluster (SMAC) organises signalling molecules for sustained T-cell activation.

Central SMAC (cSMAC): TCR–pMHC complexes, CD3 signalling complex, co-stimulatory receptors (CD28), PKCθ
Peripheral SMAC (pSMAC): LFA-1–ICAM-1 adhesion ring — stabilises cell–cell contact
Distal SMAC (dSMAC): Large phosphatase CD45 — excluded from cSMAC to permit kinase-mediated signalling

TCR Signalling Cascade

TCR engagement triggers a phosphorylation cascade initiated by the Src-family kinase Lck (associated with CD4/CD8 co-receptors):

Lck phosphorylates ITAMs on CD3ζ chains → recruitment and activation of ZAP-70
ZAP-70 phosphorylates adaptor proteins LAT and SLP-76 → activation of PLCγ1, Ras-MAPK, and PI3K-Akt pathways
PLCγ1 cleaves PIP₂ → IP₃ (Ca²⁺ release → NFAT activation) + DAG (PKCθ → NF-κB; RasGRP → AP-1)
Transcription factors NFAT, NF-κB, and AP-1 cooperatively drive IL-2 production, proliferation, and effector differentiation

⚠️

MHC restriction: T cells are MHC-restricted — a given T cell recognises antigen only in the context of the specific MHC alleles expressed on the APC. This principle, discovered by Zinkernagel and Doherty (Nobel Prize, 1996), underpins transplant rejection (recipient T cells recognise donor MHC) and explains why HLA-matching is critical in haematopoietic stem cell transplantation performed at Australian transplant centres.

HLA Polymorphism and Disease Association

The extreme polymorphism of MHC genes (HLA) in the human population is maintained by balancing selection driven by pathogen diversity. Certain HLA alleles confer disease susceptibility through altered peptide presentation:

HLA Allele	Associated Disease	Mechanism
HLA-B27	Ankylosing spondylitis, reactive arthritis	Presentation of arthritogenic peptides; misfolding triggers UPR/IL-23
HLA-DRB104:01/04:04	Rheumatoid arthritis	Shared epitope binds citrullinated peptides → anti-CCP antibodies
HLA-DQ2/DQ8	Coeliac disease	Presentation of deamidated gliadin peptides to CD4⁺ T cells
HLA-B*57:01	Abacavir hypersensitivity	Altered peptide repertoire presentation → HLA-restricted drug reaction
HLA-B*15:02	Carbamazepine-induced SJS/TEN	Drug–peptide–HLA complex activates cytotoxic T cells

🔴

Pharmacogenomic screening in Australia: HLA-B*57:01 testing is mandatory before initiating abacavir (PBS requirement) in all Australian patients. HLA-B*15:02 screening is recommended before carbamazepine in patients of Southeast Asian descent. These tests are available through major Australian pathology laboratories (MBS item 71152 — HLA typing).

T Cell Activation

Full T-cell activation requires the integration of multiple signals delivered at the immunological synapse. The classical two-signal model has been expanded to include a third signal (cytokine polarisation) that determines the effector fate of the activated T cell.

Three-Signal Model of T-Cell Activation

Signal 1

Antigen Recognition

TCR binds cognate peptide–MHC complex. CD4 or CD8 co-receptor engages MHC class II or I respectively, recruiting Lck to phosphorylate CD3 ITAMs. Alone, this signal induces anergy or apoptosis.

Specificity determinant

Signal 2

Co-stimulation

CD28 on T cell binds B7-1 (CD80) or B7-2 (CD86) on mature APC. This lowers activation threshold, promotes IL-2 production, prevents anergy, and enhances survival via Bcl-xL upregulation.

Activation threshold

Signal 3

Cytokine Polarisation

APC-derived cytokines direct CD4⁺ T-cell differentiation: IL-12 → Th1; IL-4 → Th2; IL-6+TGF-β → Th17; TGF-β+IL-2 → Treg; IL-6+IL-21 → Tfh.

Effector fate

Co-stimulatory and Co-inhibitory Receptors

T-Cell Receptor	Ligand on APC	Signal Type	Clinical Target
CD28	CD80 (B7-1), CD86 (B7-2)	Co-stimulatory	Abatacept (CTLA-4-Ig) — blocks CD80/86; used in RA (PBS listed)
CTLA-4	CD80, CD86 (higher affinity)	Co-inhibitory	Ipilimumab (anti-CTLA-4) — checkpoint inhibitor in melanoma (PBS authority)
PD-1	PD-L1 (B7-H1), PD-L2	Co-inhibitory	Nivolumab, pembrolizumab (anti-PD-1) — melanoma, NSCLC, RCC (PBS listed)
ICOS	ICOS-L (B7-H2)	Co-stimulatory	Essential for Tfh function and germinal centre responses
LAG-3	MHC class II	Co-inhibitory	Relatlimab — approved in combination with nivolumab for melanoma
TIM-3	Galectin-9, CEACAM1	Co-inhibitory	Under investigation in clinical trials for solid tumours

CD4⁺ T-Helper Cell Subsets

Following activation, CD4⁺ T cells differentiate into functionally distinct subsets determined by Signal 3 cytokines:

Subset	Master TF	Key Cytokines	Function	Pathology if Dysregulated
Th1	T-bet	IFN-γ, TNF-α, IL-2	Macrophage activation; intracellular pathogens	Organ-specific autoimmunity (MS, T1DM)
Th2	GATA-3	IL-4, IL-5, IL-13	B-cell help; helminth defence	Allergic disease, asthma
Th17	RORγt	IL-17A, IL-17F, IL-22	Neutrophil recruitment; extracellular bacteria, fungi	Psoriasis, RA, IBD
Tfh	Bcl-6	IL-21, IL-4	Germinal centre B-cell help; antibody affinity maturation	Autoantibody production; angioimmunoblastic lymphoma
Treg	FoxP3	IL-10, TGF-β, IL-35	Immune suppression; self-tolerance	IPEX syndrome (loss of FoxP3); reduced antitumour immunity

CD8⁺ T-Cell Activation and Effector Functions

CD8⁺ cytotoxic T lymphocytes (CTLs) are activated by pMHC class I on any nucleated cell (direct presentation) or on cross-presenting cDC1 (cross-presentation). Full activation requires:

TCR–pMHC class I engagement (Signal 1)
CD28 co-stimulation (Signal 2) — typically from the cross-presenting DC
CD4⁺ T-cell help — CD4⁺ T cells "license" DCs via CD40L–CD40 interaction, upregulating CD80/86 and cytokine production on the DC

CTL effector mechanisms include perforin/granzyme-mediated cytotoxicity (granule exocytosis pathway) and Fas–FasL interaction (death receptor pathway). These mechanisms are central to antiviral immunity and tumour immunosurveillance — and are the basis of checkpoint inhibitor and CAR-T-cell therapy efficacy.

T-Cell Anergy and Peripheral Tolerance

⚠️

Anergy induction: When TCR engagement (Signal 1) occurs without co-stimulation (Signal 2), the T cell enters a state of functional unresponsiveness termed anergy. This is a critical mechanism of peripheral tolerance to self-antigens presented by non-activated APCs. Anergic T cells fail to produce IL-2 and cannot proliferate upon subsequent stimulation. Therapeutically, abatacept (CTLA-4-Ig; PBS-listed for rheumatoid arthritis) exploits this mechanism by binding CD80/86 and preventing CD28 co-stimulation, thereby promoting T-cell anergy in the context of chronic autoimmune stimulation.

Clinical Applications in Australia

Vaccination: All National Immunisation Programme vaccines depend on APC-mediated T-cell activation. Adjuvants (AS01, AS04, MF59, aluminium salts) enhance DC maturation and antigen presentation. Live vaccines (MMR, varicella) provide sustained antigen presentation; inactivated vaccines require adjuvants to compensate for lack of endogenous antigen production.
Checkpoint immunotherapy: Anti-PD-1 (nivolumab, pembrolizumab) and anti-CTLA-4 (ipilimumab) antibodies release the co-inhibitory brake on T cells, restoring effector function against tumour cells. Available via PBS authority for melanoma, NSCLC, RCC, and other indications at Australian cancer centres.
Transplant immunology: Donor APCs (passenger leucocytes) present alloantigens to recipient T cells (direct allorecognition), while recipient APCs process donor MHC molecules (indirect allorecognition). Both pathways drive acute rejection; immunosuppressive regimens (tacrolimus, mycophenolate, corticosteroids) target T-cell activation downstream of antigen presentation.
Primary immunodeficiency: MHC class II deficiency (bare lymphocyte syndrome type II, caused by mutations in CIITA, RFXANK, RFX5, or RFXAP) presents in infancy with severe combined immunodeficiency and requires haematopoietic stem cell transplantation — available at Australian paediatric transplant centres (Sydney Children's Hospital, RCH Melbourne).

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

Infectious disease burden

Aboriginal and Torres Strait Islander Australians experience disproportionate burden of infections requiring robust APC-mediated T-cell responses, including chronic hepatitis B (6× prevalence vs non-Indigenous Australians), invasive pneumococcal disease, rheumatic heart disease (post-streptococcal), and tuberculosis in remote Northern Territory communities. Effective antigen presentation underpins vaccine efficacy and natural immunity to these pathogens.

Vaccine responsiveness

Optimal APC function is essential for responses to vaccines in the National Immunisation Programme. Ensuring adequate DC activation through appropriate adjuvant-containing vaccines (e.g., Boostrix®, Prevenar 13®, Shingrix®) is critical. Outreach immunisation programmes in remote communities must account for cold-chain maintenance and timely delivery.

HLA diversity

Aboriginal and Torres Strait Islander populations have distinct HLA allele frequencies that may influence disease susceptibility, vaccine responses, and transplant outcomes. Limited population-specific HLA association data exist — further research is needed. HLA-B*57:01 testing for abacavir hypersensitivity applies equally in this population.

Autoimmune and inflammatory disease

Rheumatic heart disease remains a major burden in Aboriginal and Torres Strait Islander communities, with aberrant antigen presentation and T-cell cross-reactivity between streptococcal M-protein and cardiac myosin playing a central pathogenic role. Biologic therapies targeting T-cell co-stimulation (abatacept) or cytokine pathways are increasingly accessible through PBS, though geographic barriers to specialist care persist.

Cancer immunotherapy access

Aboriginal and Torres Strait Islander Australians have lower rates of checkpoint inhibitor use despite higher incidence of some cancers. Barriers include geographic remoteness from tertiary cancer centres, delayed diagnosis, and systemic factors. Ensuring equitable access to immunotherapy that harnesses antigen presentation pathways is a priority under the National Aboriginal and Torres Strait Islander Cancer Framework.

Environmental factors

High rates of scabies, strongyloidiasis, and other parasitic infections in remote communities drive chronic Th2-skewed immune responses that may modulate APC function and impair Th1-mediated immunity to intracellular pathogens (e.g., TB). Addressing environmental health (housing, sanitation) is essential to optimise immune function.

📚 References

1. Murphy K, Weaver C. Janeway's Immunobiology. 10th ed. New York: Garland Science; 2022.
2. Joffre OP, Segura E, Savina A, Amigorena S. Cross-presentation by dendritic cells. Nature Reviews Immunology. 2012;12(8):557–569.
3. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392(6673):245–252.
4. Neefjes J, Jongsma MLM, Paul P, Bakke O. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nature Reviews Immunology. 2011;11(12):823–836.
5. Smith-Garvin JE, Koretzky GA, Jordan MS. T cell activation. Annual Review of Immunology. 2009;27:591–619.
6. Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nature Reviews Immunology. 2013;13(4):227–242.
7. Australian Technical Advisory Group on Immunisation (ATAGI). Australian Immunisation Handbook. Australian Government Department of Health; 2023. Available at: immunisationhandbook.health.gov.au.
8. Mallal S, Phillips E, Carosi G, et al. HLA-B*5701 screening for hypersensitivity to abacavir. New England Journal of Medicine. 2008;358(6):568–579.
9. Reith W, LeibundGut-Landmann S, Waldburger JM. Regulation of MHC class II gene expression by the class II transactivator. Nature Reviews Immunology. 2005;5(10):793–806.
10. Merad M, Sathe P, Helft J, Miller J, Mortha A. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annual Review of Immunology. 2013;31:563–604.
11. Australian Institute of Health and Welfare (AIHW). Aboriginal and Torres Strait Islander Health Performance Framework 2023. Canberra: AIHW; 2023.
12. Sharpe AH, Pauken KE. The diverse functions of the PD1 inhibitory pathway. Nature Reviews Immunology. 2018;18(3):153–167.