GO:0002747 antigen processing and presentation following phagocytosis: Phagolysosomal Antigen Presentation Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0002747 describes the biological process in which antigens taken up by phagocytosis are processed and presented to T cells.
• Phagocytosis delivers extracellular material into phagosomes that mature into phagolysosomes, where antigen degradation and loading onto MHC molecules occur.
• Rab17 mediates differential sorting of antigens after efferocytosis versus phagocytosis, influencing cross-presentation.
• LC3-associated phagocytosis (LAP) is a specialized pathway that intersects with antigen presentation and can be studied using established protocols.
• CD47 is a key 'don't eat me' signal that regulates phagocytosis and is a major target in cancer immunotherapy [1,2].
• Defects in phagocytic function, as seen in monocytes/macrophages, impair antigen processing and presentation and contribute to immune dysfunction.
Description
Antigen processing and presentation following phagocytosis (GO:0002747) is a specialized biological process in which professional phagocytes, such as macrophages and dendritic cells, internalize antigens via phagocytosis and subsequently process them for presentation to T lymphocytes. This pathway is essential for initiating adaptive immune responses against pathogens and tumors, and for maintaining tolerance to self-antigens. The process begins with the recognition and engulfment of particulate antigens, followed by phagosome maturation, antigen degradation, and loading of antigenic peptides onto major histocompatibility complex (MHC) molecules. Research into this pathway has revealed critical roles for Rab GTPases, such as Rab17, in sorting antigens following efferocytosis and phagocytosis. Additionally, LC3-associated phagocytosis (LAP) has emerged as a key mechanism that couples phagocytosis to antigen presentation, with protocols available for its analysis. Understanding GO:0002747 is therefore central to immunology, vaccine development, and cancer immunotherapy, where modulating phagocytic activity can enhance or suppress immune responses [1,2].
antigen processing and presentation following phagocytosis At A Glance
| GO ID | GO:0002747 |
|---|---|
| GO term | antigen processing and presentation following phagocytosis |
| Ontology | biological_process |
| Synonym | None |
| Major function | Uptake of particulate antigens via phagocytosis and their processing for MHC presentation to T cells |
| Related process | Phagosome maturation, phagolysosome formation, cross-presentation |
| Key regulators | Rab17, LC3, CD47 [1,4,6] |
| Cell types | Macrophages, dendritic cells, monocytes |
What Is GO:0002747?
GO:0002747, antigen processing and presentation following phagocytosis, is defined as the antigen processing and presentation that is initiated by the uptake of antigen via phagocytosis. In other words, it encompasses all molecular events from the phagocytic engulfment of particulate material to the display of processed antigenic peptides on the cell surface in the context of MHC molecules, thereby enabling T cell recognition.
Why Is antigen processing and presentation following phagocytosis Important in Cell Biology?
This process is fundamental to host defense, as it allows the immune system to sample and respond to particulate antigens from pathogens, dying cells, and tumors. It is also critical for the development of effective vaccines and immunotherapies, where targeting phagocytic pathways can boost antigen presentation and T cell activation [1,2]. Dysregulation of this pathway contributes to autoimmunity, chronic infections, and cancer immune evasion [1,6].
• Enables T cell activation against pathogens and tumors by presenting phagocytosed antigens.
• Plays a key role in cross-presentation, where exogenous antigens are presented on MHC class I to CD8+ T cells.
• Regulated by Rab17, which sorts antigens differentially after efferocytosis versus phagocytosis.
• LC3-associated phagocytosis (LAP) is a specialized pathway that can enhance antigen presentation.
• CD47-SIRPα signaling inhibits phagocytosis and is a major immune checkpoint in cancer.
• Antibody-toxin conjugates targeting CD47 can promote phagocytosis and antitumor immunity.
• Defects in monocyte/macrophage phagocytosis lead to impaired antigen presentation and immunodeficiency.
• Environmental toxins like paraquat can dysregulate microglial antigen processing, linking to neuroimmunotoxicity.
• Targeting CD37 enhances macrophage-dependent phagocytosis of cancer cells, offering a therapeutic strategy.
• Understanding this process aids in designing vaccines that efficiently deliver antigens to phagocytes.
What Happens During antigen processing and presentation following phagocytosis?
Phagocytic uptake of antigen
In simple terms: The cell engulfs particles like bacteria or dead cells.
The process begins when phagocytes recognize and bind particulate antigens via receptors, leading to actin-dependent engulfment and formation of a phagosome. This step is regulated by signals such as CD47, which acts as a 'don't eat me' signal, and its blockade enhances phagocytosis. Targeting CD47 with antibody-toxin conjugates has been shown to promote phagocytosis in cancer immunotherapy.
Phagosome maturation and antigen degradation
In simple terms: The engulfed particle is digested inside the cell.
The nascent phagosome undergoes maturation by fusing with endosomes and lysosomes, becoming increasingly acidic and acquiring proteolytic enzymes that degrade the antigen into peptides. This maturation process is essential for generating antigenic peptides suitable for MHC loading. Rab17 has been implicated in differential sorting of antigens following efferocytosis and phagocytosis, influencing the fate of internalized material.
Antigen loading onto MHC molecules
In simple terms: Pieces of the digested antigen are loaded onto special carrier molecules.
Peptides generated in the phagolysosome are loaded onto MHC class II molecules, or in the case of cross-presentation, onto MHC class I molecules. This loading occurs in specialized compartments and is facilitated by chaperones such as HLA-DM. The route of antigen delivery can affect whether presentation occurs on MHC I or MHC II, with Rab17 playing a role in this sorting decision.
Presentation to T cells and immune activation
In simple terms: The loaded carrier moves to the cell surface to show the antigen to immune cells.
MHC-peptide complexes are transported to the plasma membrane where they are presented to T cells, leading to T cell activation if the appropriate costimulatory signals are present. This step is the culmination of the pathway and is critical for initiating adaptive immune responses. LC3-associated phagocytosis (LAP) can enhance this process by promoting antigen presentation.
Regulation by Rab GTPases and LAP
In simple terms: Traffic controllers and recycling systems fine-tune the process.
Rab17 mediates differential antigen sorting following efferocytosis and phagocytosis, directing antigens toward distinct presentation pathways. LC3-associated phagocytosis (LAP) is a specialized form of phagocytosis that recruits LC3 to the phagosome and can influence antigen presentation. These regulatory mechanisms ensure appropriate immune responses to different types of cargo [4,6].
Key Genes Involved in GO:0002747 antigen processing and presentation following phagocytosis
The following genes and proteins are central to antigen processing and presentation following phagocytosis, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CD47 | 'Don't eat me' signal that inhibits phagocytosis | Target for cancer immunotherapy to enhance phagocytosis [1,2] |
| Rab17 | Mediates differential antigen sorting after efferocytosis and phagocytosis | Regulates cross-presentation and immune tolerance |
| LC3 | Recruited to phagosomes in LC3-associated phagocytosis (LAP) | Links autophagy machinery to antigen presentation |
| CD37 | Tetraspanin that regulates macrophage phagocytosis | Targeting CD37 promotes tumor clearance |
| MHC class I | Presents endogenous and cross-presented antigens to CD8+ T cells | Central to cross-presentation following phagocytosis |
| MHC class II | Presents exogenous antigens to CD4+ T cells | Key for antigen presentation after phagocytosis |
| HLA-DM | Catalyzes peptide loading onto MHC class II | Facilitates antigen processing in phagolysosomes |
| SIRPα | Receptor for CD47 that inhibits phagocytosis | Immune checkpoint in cancer |
| Listeriolysin O | Bacterial toxin used in antibody-toxin conjugates | Enhances phagocytosis and antigen presentation |
| TLR2 | Recognizes microbial components and promotes phagocytosis | Innate immune sensor linked to antigen presentation |
| TLR4 | Activates phagocytes upon LPS recognition | Enhances antigen processing |
| Fcγ receptors | Mediate antibody-dependent phagocytosis | Important for opsonin-mediated antigen uptake |
| Complement receptor 3 | Binds complement-coated particles for phagocytosis | Alternative route for antigen internalization |
| Cathepsins | Proteases that degrade antigens in phagolysosomes | Generate peptides for MHC loading |
| V-ATPase | Acidifies phagosomes | Required for phagosome maturation and antigen degradation |
| Rab5 | Early endosome marker involved in phagosome maturation | Regulates phagosome fusion |
| Rab7 | Late endosome/lysosome marker | Promotes phagolysosome formation |
How Is antigen processing and presentation following phagocytosis Regulated?
The process of antigen processing and presentation following phagocytosis is tightly regulated at multiple levels. CD47-SIRPα signaling acts as a checkpoint to inhibit phagocytosis, and blockade of this interaction enhances antigen uptake and presentation. Rab17 mediates differential sorting of antigens following efferocytosis versus phagocytosis, thereby regulating the balance between tolerance and immunity. LC3-associated phagocytosis (LAP) is a specialized pathway that can be induced by Toll-like receptor signaling and influences antigen presentation. Additionally, environmental factors such as paraquat can dysregulate microglial antigen processing, highlighting the sensitivity of this pathway to external stressors.
antigen processing and presentation following phagocytosis and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CD47 | Cancer immune evasion | CD47 knockout tumor cells or anti-CD47 antibody treatment in mouse models [1,2] |
| Rab17 | Altered cross-presentation and autoimmunity | Rab17 knockout mice or knockdown in dendritic cells |
| CD37 | Lymphoma and solid tumors | CD37 knockout mice or anti-CD37 antibody therapy |
| LC3 | Impaired LAP and antigen presentation | LC3 knockout macrophages or LAP-deficient mice |
| Paraquat exposure | Neuroimmunotoxicity | Microglial cells treated with paraquat in vitro |
Cancer immune evasion
Tumors often overexpress CD47 to evade phagocytosis by macrophages, thereby limiting antigen presentation and T cell activation. Targeting CD47 with blocking antibodies or antibody-toxin conjugates can restore phagocytosis and promote antitumor immunity. Similarly, targeting CD37 enhances macrophage-dependent phagocytosis of cancer cells and facilitates tumor clearance in preclinical models.
Neuroimmunotoxicity and neurodegeneration
Dysregulated microglial antigen processing following exposure to environmental toxins such as paraquat can contribute to neuroinflammation and neuroimmunotoxicity. This suggests that impaired phagocytic antigen presentation in the brain may play a role in neurodegenerative diseases.
Immunodeficiency and phagocytic defects
Defects in monocyte/macrophage phagocytosis lead to impaired antigen processing and presentation, resulting in increased susceptibility to infections. Such defects are observed in various primary immunodeficiencies and can be studied using patient-derived cells.
From antigen processing and presentation following phagocytosis-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does CD47 knockout enhance phagocytosis and antigen presentation? | CD47 knockout cell lines or mice |
| What is the role of Rab17 in antigen sorting after phagocytosis? | Rab17 knockout or knockdown dendritic cells |
| Can targeting CD37 improve tumor clearance? | CD37 knockout mice or anti-CD37 antibodies in tumor models |
| How does LC3-associated phagocytosis affect antigen presentation? | LC3 knockout macrophages or LAP inhibitors |
| Does paraquat exposure alter microglial antigen processing? | Primary microglia or microglial cell lines treated with paraquat |
| Are phagocytic defects responsible for immunodeficiency? | Patient-derived monocytes/macrophages from immunodeficient individuals |
How to Study the antigen processing and presentation following phagocytosis Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Flow cytometry phagocytosis assay | Uptake of fluorescent particles or bacteria | Screening for phagocytosis enhancers or inhibitors |
| LC3 recruitment assay | LC3 lipidation on phagosomes | Studying LAP |
| Antigen presentation assay | T cell activation by MHC-peptide complexes | Evaluating cross-presentation |
| Confocal microscopy | Colocalization of antigens with MHC and Rab GTPases | Tracking antigen sorting |
| Cytokine profiling | Inflammatory mediators released by phagocytes | Assessing neuroimmunotoxicity |
| Western blot | Protein expression and signaling | Validating knockout or knockdown |
| RNA sequencing | Transcriptional changes during phagocytosis | Identifying novel regulators |
Analysis of LC3-associated phagocytosis and antigen presentation
Ligeon et al. provide a detailed protocol for analyzing LC3-associated phagocytosis and its impact on antigen presentation, including microscopy and flow cytometry-based assays. This method allows researchers to track the recruitment of LC3 to phagosomes and assess subsequent antigen presentation to T cells.
Tracking antigen sorting with Rab17
Yin et al. used imaging and biochemical approaches to demonstrate that Rab17 mediates differential antigen sorting following efferocytosis and phagocytosis. This includes pulse-chase experiments and colocalization studies to determine the fate of internalized antigens.
Evaluating phagocytosis and antigen presentation in cancer models
In cancer immunotherapy research, phagocytosis is often assessed using flow cytometry-based phagocytosis assays, and antigen presentation is measured by T cell activation assays [1,2]. These methods can be applied to evaluate the efficacy of CD47-targeted therapies [1,2].
Assessing microglial antigen processing
Shi et al. investigated paraquat-induced neuroimmunotoxicity by analyzing microglial antigen processing using flow cytometry and cytokine profiling. This approach can be adapted to study other environmental toxins.
How CRISPR Can Be Used to Study GO:0002747 antigen processing and presentation following phagocytosis
Knockout
CRISPR knockout of genes such as CD47, Rab17, or CD37 can be used to study their roles in antigen processing and presentation following phagocytosis [1,6,8]. For example, CD47 knockout cells show enhanced phagocytosis and antigen presentation.
Point Mutation
Introducing point mutations in genes like Rab17 can help dissect specific domains required for antigen sorting. This approach allows fine-tuning of protein function without complete loss of expression.
Knock-in
Knock-in of tagged versions of LC3 or MHC molecules can facilitate live-cell imaging of phagosome maturation and antigen loading. This enables real-time tracking of the pathway.
Overexpression
Overexpression of CD47 or its ligand SIRPα can be used to study immune evasion mechanisms. Conversely, overexpression of Rab17 can enhance cross-presentation.
How EDITGENE Supports antigen processing and presentation following phagocytosis Research
Researchers studying antigen processing and presentation following phagocytosis-related genes often need to determine whether a candidate gene is causally involved in phagocytosis, antigen processing, or T cell activation. EDITGENE provides comprehensive CRISPR-based services to create precisely engineered cell models for such investigations.
Contact EDITGENE today to design your custom CRISPR model for antigen processing and presentation following phagocytosis research.
Frequently Asked Questions About antigen processing and presentation following phagocytosis
What is antigen processing and presentation following phagocytosis?
It is the biological process (GO:0002747) in which antigens taken up by phagocytosis are processed and presented to T cells, typically by macrophages and dendritic cells.
What genes are involved in antigen processing and presentation following phagocytosis?
Key genes include CD47, Rab17, LC3, CD37, MHC class I and II, and various Rab GTPases [1,4,6,8].
How does phagocytosis lead to antigen presentation?
After engulfment, the phagosome matures and fuses with lysosomes, where antigens are degraded into peptides that load onto MHC molecules for presentation.
What is the role of Rab17 in antigen presentation?
Rab17 mediates differential sorting of antigens following efferocytosis and phagocytosis, influencing whether antigens are cross-presented or presented on MHC II.
What is LC3-associated phagocytosis?
LC3-associated phagocytosis (LAP) is a specialized pathway where LC3 is recruited to phagosomes, enhancing antigen presentation.
How is CD47 involved in phagocytosis?
CD47 acts as a 'don't eat me' signal; blocking CD47 enhances phagocytosis and antigen presentation, making it a target for cancer immunotherapy [1,2].
Can defects in phagocytosis cause disease?
Yes, defects in monocyte/macrophage phagocytosis can lead to impaired antigen presentation and immunodeficiency.
What diseases are linked to dysregulated phagocytic antigen presentation?
Cancer immune evasion, neuroimmunotoxicity, and primary immunodeficiencies are linked to dysregulation of this process [1,3,7].
How can I study antigen processing and presentation following phagocytosis?
Common methods include flow cytometry phagocytosis assays, LC3 recruitment assays, antigen presentation assays, and microscopy [4,6].
What CRISPR models are available for studying this process?
Knockout, point mutation, knock-in, and overexpression models can be generated for genes like CD47, Rab17, and LC3 [1,4,6].
Conclusion
Antigen processing and presentation following phagocytosis (GO:0002747) is a cornerstone of adaptive immunity, enabling the immune system to respond to particulate antigens from pathogens and tumors. Key regulators such as CD47, Rab17, and LC3 modulate this pathway and represent promising therapeutic targets [1,4,6]. Understanding the molecular mechanisms and disease implications of this process is essential for developing vaccines and immunotherapies. EDITGENE provides advanced CRISPR tools to facilitate research in this field.
References
- 1. Liu Y et al.. 2024. Deciphering the role of CD47 in cancer immunotherapy.. J Adv Res 63:129-158 PMID: 39167629
- 2. Schrank BR et al.. 2025. An antibody-toxin conjugate targeting CD47 linked to the bacterial toxin listeriolysin O for cancer immunotherapy.. Nat Cancer 6(3):511-527 PMID: 40000910
- 3. Shi G et al.. 2025. Paraquat induced neuro-immunotoxicity: Dysregulated microglial antigen processing and mitochondrial activated mechanisms.. Chem Biol Interact 421:111721 PMID: 40912350
- 4. Ligeon LA et al.. 2017. Analysis of LC3-Associated Phagocytosis and Antigen Presentation.. Methods Mol Biol 1519:145-168 PMID: 27815878
- 5. Mellman I. 1990. Endocytosis and antigen processing.. Semin Immunol 2(4):229-37 PMID: 1983336
- 6. Yin C et al.. 2016. Rab17 mediates differential antigen sorting following efferocytosis and phagocytosis.. Cell Death Dis 7(12):e2529 PMID: 28005073
- 7. Douglas SD et al.. 1986. Phagocytic defects--monocytes/macrophages.. Clin Immunol Immunopathol 40(1):62-8 PMID: 3521970
- 8. Gao X et al.. 2025. Targeting CD37 promotes macrophage-dependent phagocytosis of multiple cancer cell types and facilitates tumor clearance in mice.. Nat Commun 16(1):6610 PMID: 40675974
