GO:1905675 negative regulation of adaptive immune memory response: Immune Regulation, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1905675 describes any biological process that stops, prevents, or reduces the frequency, rate, or extent of adaptive immune memory response.
• Adaptive immune memory is the basis of long-lived protection after infection or vaccination, and its negative regulation is essential to prevent immunopathology and autoimmunity.
• Checkpoint molecules such as PD-1 and cytokines such as IL-1 family members can suppress memory T cell reactivation and effector recall.
• Tumor-associated macrophages and fibroblast lineages can restrain anti-tumor memory responses through immunosuppressive reprogramming.
• Glyco-immune barriers, such as sialylated CD43, can limit antileukemic immunity and memory formation.
• CRISPR knockout, point mutation, knock-in, and overexpression models enable causal dissection of negative regulators of immune memory.
Description
Adaptive immune memory is the hallmark of vertebrate immunity, enabling faster and stronger responses upon re-exposure to a pathogen. However, unchecked memory responses can cause tissue damage, autoimmunity, and chronic inflammation. The Gene Ontology term GO:1905675, negative regulation of adaptive immune memory response, captures the processes that stop, prevent, or reduce the frequency, rate, or extent of this memory response. Understanding these brakes is critical for vaccine design, cancer immunotherapy, and treatment of autoimmune diseases. Recent studies show that negative regulation occurs at multiple levels, including checkpoint receptor signaling, cytokine networks, and metabolic or glyco-immune barriers. For example, PD-1 blockade relieves inhibition of adaptive immune resistance in tumors, demonstrating that removing negative regulation can restore effective immunity. Similarly, IL-1 family cytokines can shape the magnitude and duration of memory responses. This article synthesizes authoritative GO annotation and verified PubMed literature to provide a research-grade overview of GO:1905675, its mechanisms, key genes, disease relevance, and experimental models.
negative regulation of adaptive immune memory response At A Glance
| GO ID | GO:1905675 |
|---|---|
| GO term | negative regulation of adaptive immune memory response |
| Ontology | biological_process |
| Synonym | down regulation of adaptive immune memory response; down-regulation of adaptive immune memory response; downregulation of adaptive immune memory response; inhibition of adaptive immune memory response |
| Major function | Suppression or termination of adaptive immune memory responses to prevent excessive inflammation and autoimmunity |
| Regulatory direction | Negative (inhibitory) |
| Target process | Adaptive immune memory response |
| Related cell types | Memory T cells, memory B cells, regulatory T cells, antigen-presenting cells |
| Disease relevance | Autoimmunity, cancer immune evasion, chronic infection, vaccine non-responsiveness |
What Is GO:1905675?
GO:1905675 is a biological process term defined as any process that stops, prevents, or reduces the frequency, rate, or extent of adaptive immune memory response. In other words, it encompasses molecular and cellular events that dampen the recall response of T and B cells after initial antigen exposure. This includes inhibition of memory T cell reactivation, suppression of antibody production by memory B cells, and active termination of memory cell survival or proliferation. The term is a negative regulatory counterpart to the positive processes that establish and maintain immune memory.
Why Is negative regulation of adaptive immune memory response Important in Cell Biology?
Negative regulation of adaptive immune memory response is essential for maintaining immune homeostasis and preventing immunopathology. Without these brakes, persistent memory responses can lead to tissue destruction, autoimmune diseases, and chronic inflammatory conditions. In cancer, tumors often exploit these negative regulatory mechanisms to evade immune memory, leading to poor responses to immunotherapy. Understanding GO:1905675 provides a framework for identifying therapeutic targets to either enhance immunity (e.g., in cancer or vaccination) or suppress it (e.g., in autoimmunity or transplant rejection).
• Prevents excessive inflammation and tissue damage after pathogen clearance.
• Limits autoimmune reactions by restraining self-reactive memory T and B cells.
• Contributes to tumor immune evasion by suppressing anti-tumor memory responses.
• Influences vaccine durability and recall responses.
• Modulates chronic infections where persistent antigen leads to memory exhaustion.
• Provides targets for checkpoint blockade in cancer immunotherapy.
• Shapes the efficacy of adoptive T cell therapies.
• Regulates the balance between protective immunity and immune pathology.
• Involved in glyco-immune barriers that restrain antileukemic immunity.
• Key for understanding fibroblast and macrophage-mediated immune suppression in tumors.
What Happens During negative regulation of adaptive immune memory response?
Initiation of negative signals
In simple terms: The immune system receives stop signals that tell memory cells to quiet down.
Negative regulation begins when inhibitory receptors such as PD-1 are engaged by their ligands on antigen-presenting cells or tumor cells. This engagement recruits phosphatases that dampen T cell receptor signaling, reducing memory T cell reactivation and effector cytokine production. Additionally, anti-inflammatory cytokines like IL-1 receptor antagonist can blunt the expansion of memory T cells.
Suppression of memory T cell reactivation
In simple terms: Memory T cells are prevented from waking up and attacking again.
Checkpoint pathways, including PD-1/PD-L1, directly inhibit the proliferation and effector function of memory T cells. In the tumor microenvironment, PD-1 blockade can reverse this suppression, restoring adaptive immune responses. Regulatory T cells also contribute by consuming IL-2 and secreting inhibitory cytokines, further limiting memory T cell reactivation.
Inhibition of memory B cell differentiation and antibody production
In simple terms: Memory B cells are stopped from turning into antibody factories.
Negative regulation can occur at the level of memory B cells by limiting their differentiation into plasma cells. This involves inhibitory signals from FcγRIIB, which co-crosslinks with the B cell receptor and dampens activation. Cytokines such as IL-1 family members can also modulate B cell memory responses.
Role of tumor-associated macrophages and fibroblasts
In simple terms: Support cells in tumors can put the brakes on immune memory.
Tumor-associated macrophages (TAMs) can be reprogrammed to an immunosuppressive phenotype that inhibits anti-tumor memory responses. Targeting USP7 in lung cancer TAMs modulates anti-tumor immune responses, highlighting a negative regulatory axis. Similarly, specific pancreatic fibroblast lineages support anti-tumor immunity, and their dysregulation may impair memory responses.
Glyco-immune barriers
In simple terms: Sugar modifications on cell surfaces can block immune memory.
Sialylated CD43 forms a glyco-immune barrier that restrains antileukemic immunity, including memory responses. This barrier can be targeted to enhance immune memory against leukemia.
Termination of memory responses
In simple terms: After the threat is gone, memory cells are instructed to die or become quiescent.
Negative regulation also includes active termination of memory responses through apoptosis of expanded memory cells or induction of exhaustion. This prevents chronic inflammation and autoimmunity. IL-1 family cytokines can influence this balance, with some members promoting resolution.
Key Genes Involved in GO:1905675 negative regulation of adaptive immune memory response
The following genes and proteins are key players in the negative regulation of adaptive immune memory response, based on verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| PDCD1 (PD-1) | Inhibitory receptor on T cells; suppresses memory T cell reactivation | Target for cancer immunotherapy; PD-1 blockade enhances anti-tumor memory |
| CD274 (PD-L1) | Ligand for PD-1; delivers inhibitory signals | Expressed on tumor cells and APCs; mediates adaptive immune resistance |
| IL1RN | IL-1 receptor antagonist; dampens IL-1 signaling | Modulates memory T cell expansion and inflammation |
| IL1B | Pro-inflammatory cytokine; can indirectly limit memory responses | Shapes the magnitude of adaptive immunity |
| USP7 | Deubiquitinase; regulates TAM polarization | Targeting USP7 reprograms TAMs and modulates anti-tumor immunity |
| CD43 (SPN) | Sialylated glycoprotein; forms glyco-immune barrier | Restrains antileukemic immunity; potential target |
| FOXP3 | Master regulator of regulatory T cells | Tregs suppress memory T cell responses |
| CTLA4 | Inhibitory receptor on T cells | Checkpoint molecule; negative regulator of memory |
| LAG3 | Inhibitory receptor | Co-inhibitory molecule limiting memory responses |
| HAVCR2 (TIM-3) | Inhibitory receptor | Associated with T cell exhaustion |
| TGFB1 | Immunosuppressive cytokine | Inhibits memory T cell proliferation |
| IL10 | Anti-inflammatory cytokine | Suppresses effector and memory responses |
| FcγRIIB (FCGR2B) | Inhibitory Fc receptor on B cells | Limits memory B cell activation |
| CD4 | Helper T cell marker | Central to memory responses; targeted by negative regulation |
| CD8 | Cytotoxic T cell marker | Memory CTLs are key targets of negative regulation |
| GZMB | Granzyme B; effector molecule | Its suppression indicates negative regulation |
| IFNG | Interferon gamma; effector cytokine | Reduced by negative regulation |
| TNF | Tumor necrosis factor | Modulated during memory suppression |
How Is negative regulation of adaptive immune memory response Regulated?
The negative regulation of adaptive immune memory response is itself tightly regulated by multiple signaling pathways. Checkpoint receptors such as PD-1 and CTLA-4 are transcriptionally induced upon T cell activation and provide negative feedback. Cytokine networks, including IL-1 family members and TGF-β, modulate the strength and duration of memory responses. Metabolic factors and the tumor microenvironment, including TAMs and fibroblasts, can also enforce negative regulation. Additionally, glyco-immune barriers like sialylated CD43 can be dynamically regulated. These layers ensure that memory responses are appropriately terminated after pathogen clearance while allowing for long-term protective immunity.
negative regulation of adaptive immune memory response and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| PDCD1 | Cancer immune evasion | PD-1 knockout mice; tumor challenge models |
| CD274 | Cancer immune evasion | PD-L1 overexpression in tumor cell lines |
| USP7 | Lung cancer | USP7 knockout or knockdown in TAMs; lung cancer models |
| SPN (CD43) | Leukemia | CD43 knockout leukemia cells; sialylation inhibitors |
| IL1RN | Autoimmune diseases | IL-1RA knockout mice; autoimmune models |
Cancer immune evasion
Tumors exploit negative regulation of adaptive immune memory to escape immune surveillance. PD-L1 expression on tumor cells engages PD-1 on memory T cells, leading to their exhaustion and reduced anti-tumor activity. Targeting this axis with checkpoint inhibitors can restore memory responses and improve clinical outcomes. Other mechanisms, such as USP7-mediated TAM reprogramming, also contribute to immune evasion.
Autoimmune diseases
Defective negative regulation can lead to excessive memory responses against self-antigens, causing autoimmune diseases such as lupus or rheumatoid arthritis. IL-1 family cytokines are implicated in shaping autoimmune memory responses. Enhancing negative regulation is a therapeutic strategy for autoimmunity.
Chronic infections
In chronic viral infections, persistent antigen leads to sustained negative regulation, resulting in T cell exhaustion and impaired memory. This is characterized by high PD-1 expression and reduced effector function. Understanding these mechanisms is crucial for developing therapies to reinvigorate exhausted T cells.
Leukemia and glyco-immune barriers
Sialylated CD43 on leukemic cells forms a glyco-immune barrier that restrains antileukemic immunity, including memory responses. Disrupting this barrier could enhance immune memory against leukemia.
From negative regulation of adaptive immune memory response-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does PD-1 negatively regulate memory T cell responses? | PDCD1 knockout mice |
| What is the role of USP7 in TAM-mediated immune suppression? | USP7 conditional knockout in macrophages |
| How does sialylated CD43 restrain antileukemic memory? | CD43 point mutant leukemia cells |
| Can IL-1RA enhance memory responses? | IL1RN overexpression in mice |
| Does fibroblast lineage support anti-tumor memory? | Fibroblast-specific knockout models |
| What is the effect of PD-L1 on memory T cells? | PD-L1 knock-in tumor cells |
How to Study the negative regulation of adaptive immune memory response Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Flow cytometry | Frequency and phenotype of memory T/B cells | Quantify antigen-specific memory responses |
| scRNA-seq | Transcriptional heterogeneity | Identify negative regulators in immune cells |
| CRISPR knockout screens | Genes that modulate immune memory | Discover negative regulators |
| Tetramer staining | Antigen-specific T cells | Monitor memory responses |
| ELISPOT | Cytokine-secreting memory cells | Assess functional memory |
| Adoptive transfer | Memory cell function in vivo | Test negative regulation in vivo |
| Western blot | Protein expression of checkpoint molecules | Validate knockout/overexpression |
| Immunohistochemistry | Tissue localization of memory cells | Study tumor microenvironment |
Flow cytometry and tetramer staining
Flow cytometry with peptide-MHC tetramers allows quantification of antigen-specific memory T cells. This method can assess the frequency and phenotype of memory cells under negative regulation, such as PD-1 expression.
Single-cell RNA sequencing
scRNA-seq reveals heterogeneity in memory T cell populations and identifies transcriptional signatures of negative regulation. It has been used to define fibroblast lineages that support anti-tumor immunity.
CRISPR screens
Genome-wide CRISPR knockout screens can identify negative regulators of adaptive immune memory. For example, targeting USP7 was found to modulate anti-tumor immune responses.
In vivo tumor models
Syngeneic tumor models and checkpoint blockade experiments are used to study negative regulation in vivo. PD-1 blockade in melanoma models demonstrates relief of adaptive immune resistance.
How CRISPR Can Be Used to Study GO:1905675 negative regulation of adaptive immune memory response
Knockout
CRISPR knockout of negative regulators such as PDCD1 or USP7 can enhance adaptive immune memory responses. For example, PD-1 knockout T cells show increased anti-tumor activity. USP7 knockout in macrophages reprograms TAMs and modulates anti-tumor immunity.
Point Mutation
Point mutations can be introduced to dissect specific domains or signaling motifs. For instance, mutating phosphorylation sites in PD-1 can reveal their role in inhibiting memory responses. Similarly, point mutations in CD43 can disrupt its sialylation and glyco-immune barrier function.
Knock-in
Knock-in of reporters or tags allows tracking of memory cells and negative regulators. For example, knocking in a fluorescent reporter into the PDCD1 locus enables visualization of PD-1 expression in vivo. Knock-in of human PD-L1 into mouse tumor cells can model human immune evasion.
Overexpression
Overexpression of negative regulators such as PD-L1 or IL-1RA can suppress adaptive immune memory. This is useful to study mechanisms of immune evasion or to model autoimmune suppression.
How EDITGENE Supports negative regulation of adaptive immune memory response Research
Researchers studying negative regulation of adaptive immune memory response-related genes often need to determine whether a candidate gene is causally involved in suppressing memory responses. This requires precise genetic models to manipulate gene function in relevant cell types, such as T cells, B cells, macrophages, and fibroblasts. EDITGENE provides a comprehensive suite of CRISPR-based services to accelerate this research.
Contact EDITGENE today to design your custom CRISPR model for negative regulation of adaptive immune memory response research.
Frequently Asked Questions About negative regulation of adaptive immune memory response
What is GO:1905675?
GO:1905675 is a Gene Ontology term for negative regulation of adaptive immune memory response, describing any process that stops, prevents, or reduces the frequency, rate, or extent of adaptive immune memory response.
What genes are involved in negative regulation of adaptive immune memory response?
Key genes include PDCD1 (PD-1), CD274 (PD-L1), USP7, IL1RN, and SPN (CD43), among others.
How does PD-1 inhibit immune memory?
PD-1 engagement by PD-L1 recruits phosphatases that dampen T cell receptor signaling, reducing memory T cell reactivation and effector function.
What diseases are linked to negative regulation of adaptive immune memory?
Cancer immune evasion, autoimmune diseases, chronic infections, and leukemia are linked to this process.
How can I study negative regulation of adaptive immune memory response?
Use CRISPR knockout, point mutation, knock-in, and overexpression models, combined with flow cytometry, scRNA-seq, and in vivo tumor models.
What is the role of USP7 in immune memory?
USP7 targeting modulates anti-tumor immune response by reprogramming tumor-associated macrophages, thereby affecting memory responses.
What is the glyco-immune barrier in leukemia?
Sialylated CD43 forms a glyco-immune barrier that restrains antileukemic immunity, including memory responses.
Which cytokines negatively regulate immune memory?
IL-1 family cytokines, including IL-1RA, and TGF-β, IL-10 can suppress memory responses.
How do regulatory T cells suppress memory responses?
Tregs consume IL-2 and secrete inhibitory cytokines, limiting memory T cell reactivation.
What CRISPR models are available for studying this process?
EDITGENE offers knockout, point mutation, knock-in, and overexpression models for genes like PDCD1, USP7, and CD43.
Conclusion
GO:1905675, negative regulation of adaptive immune memory response, is a critical biological process that balances protective immunity with immune homeostasis. Dysregulation of this process contributes to cancer, autoimmunity, and chronic infections. Advances in CRISPR genome editing and single-cell technologies are enabling precise dissection of the molecular players involved. EDITGENE provides comprehensive services to support research on this important pathway, from knockout models to CRISPR library screening.
References
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- 4. Hutton C et al.. 2021. Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity.. Cancer Cell 39(9):1227-1244.e20 PMID: 34297917
- 5. Garlanda C et al.. 2013. The interleukin-1 family: back to the future.. Immunity 39(6):1003-18 PMID: 24332029
- 7. Chung J et al.. 2026. Sialylated CD43 forms a glyco-immune barrier that restrains antileukemic immunity.. Science 392(6794):eady5196 PMID: 41955354
- 8. Dai X et al.. 2020. USP7 targeting modulates anti-tumor immune response by reprogramming Tumor-associated Macrophages in Lung Cancer.. Theranostics 10(20):9332-9347 PMID: 32802195
