Anti-Mouse CD122 (IL-2Rβ) – Purified in vivo GOLD™ Functional Grade

Clone TM-?1 is a monoclonal antibody that targets mouse CD122 (IL-2/IL-15 receptor ? chain) and is widely used in in vivo mouse studies to block signaling through the IL-2 and IL-15 pathways. This antibody is typically administered via intraperitoneal (i.p.) injection and used for a range of immunological interventions.

Key uses in in vivo mouse studies include:

• Blockade of IL-2 and IL-15 signaling: TM-?1 is used to block the interaction of IL-2 and IL-15 with their shared receptor component CD122, thereby inhibiting downstream signaling. This is used to study the role of these cytokines in immune cell survival, proliferation, and function.
• Depletion of CD122+ cell populations: Administration of TM-?1 leads to the depletion of CD122-expressing cells, such as NK cells and subsets of CD8+ T cells, depending on the dosing regimen. The antibody can markedly reduce these populations in blood and tissues.
• Therapeutic intervention in disease models: In models of autoimmune disease (e.g., diabetes in NOD mice, inflammatory bowel disease), TM-?1 treatment can suppress disease progression by reversing lymphoid proliferation, reducing inflammatory infiltrates, and restoring tissue architecture.
• Dosing and administration: Protocols vary, but studies commonly use repeated i.p. injections (e.g., weekly or biweekly) over several weeks to maintain blockade. Quantities are typically in the range of 100 ?g/mouse per injection, though this can be adjusted based on experimental design.
• Monitoring effects: Efficacy is assessed by measuring immune cell subsets (by flow cytometry), histological analysis of target tissues, and disease endpoints relevant to the experimental model.

In summary, TM-?1 is an anti-mouse CD122 antibody used in vivo to block IL-2/IL-15 signaling, deplete CD122+ cell subsets, and modulate immune responses in disease models.

Commonly Used Antibodies and Proteins Alongside TM-?1 in the Literature

TM-?1 is a well-characterized monoclonal antibody that specifically targets murine CD122 (IL-2R?), a subunit shared by the receptors for both IL-2 and IL-15, and is widely used to block IL-2 and IL-15 signaling in immunology research. In various studies, TM-?1 has been used in combination with other antibodies, cytokines, or proteins to investigate immune regulation, tolerance, and autoimmune disease models.

Frequent Combinations with TM-?1

• Anti-CD25 (IL-2R?) Antibodies: In studies investigating IL-2 and IL-15 signaling, antibodies against CD25 (the alpha subunit of the IL-2 receptor) are often used to distinguish the effects of high-affinity (CD25/CD122/CD132) versus intermediate-affinity (CD122/CD132) receptor complexes. However, TM-?1 itself does not block signaling through the high-affinity IL-2 receptor (which requires CD25), but it effectively blocks IL-15 trans-presentation and IL-2 signaling in cells lacking CD25.
• Cytokines:
  • IL-2 (Interleukin-2): TM-?1 is sometimes used in conjunction with recombinant IL-2 to study T regulatory cell (Treg) expansion and function, particularly in settings where the goal is to differentiate between IL-2 signaling via high- versus intermediate-affinity receptors.
  • IL-33: In combinatorial immunotherapy studies, IL-33 is administered alongside TM-?1 to assess its synergistic effects on Treg function and immune tolerance, especially since tissue Tregs express high levels of IL-33 receptor (ST2).
• Other Anti-CD122 Antibodies (e.g., ChMBC7): ChMBC7 is another anti-mouse CD122 antibody used in parallel with TM-?1 to confirm findings or compare blocking efficiencies in both in vitro and in vivo settings.
• Control Antibodies: Isotype-matched control antibodies (e.g., rat IgG) are routinely used as negative controls in TM-?1 experiments to ensure specificity.
• Flow Cytometry Markers: In flow cytometry, TM-?1 is often paired with fluorescently labeled antibodies against other cell surface markers (e.g., CD3, CD4, CD8, CD44, NK1.1) to phenotype immune cell populations affected by IL-2 or IL-15 blockade.

Key Experimental Contexts

• Autoimmunity and Tolerance: TM-?1 is frequently combined with cytokines (IL-2, IL-33) to evaluate their combined impact on Treg abundance and function in autoimmune models such as non-obese diabetic (NOD) mice.
• Proliferation Assays: In assays measuring cell proliferation (e.g., CTLL-2 cells), TM-?1 is used to block IL-2 or IL-15 signaling, often in the presence of these cytokines to assess receptor-specific effects.
• Phenotyping Immune Subsets: TM-?1-treated animals are commonly analyzed using a panel of antibodies for CD8, CD44, NK1.1, and other markers to assess changes in memory T cells, NK cells, and other lymphocyte subsets.

Table: Examples of Antibodies and Proteins Used with TM-?1

Summary

TM-?1 is most commonly paired with anti-CD25 antibodies, recombinant IL-2 and IL-33 cytokines, and other anti-CD122 antibodies like ChMBC7 for mechanistic studies in immunology. Flow cytometry panels for immune cell phenotyping and isotype control antibodies are standard accompaniments in these experiments. The choice of combination depends on the specific research question—whether focusing on receptor signaling, immune cell subsets, or therapeutic interventions in autoimmunity.

Clone TM-?1 represents a significant research tool in immunology and autoimmune disease studies, with several key findings emerging from scientific literature regarding its therapeutic potential and mechanisms of action.

Primary Mechanism and Target

TM-?1 is a monoclonal antibody that specifically binds to the murine IL-2/IL-15R? (CD122) receptor, effectively blocking IL-15 signaling pathways. This antibody has proven highly effective in suppressing IL-15 activity, which plays a crucial role in maintaining and expanding certain immune cell populations, particularly NK cells and memory CD8+ T cells.

Effects on Immune Cell Populations

NK Cell Elimination: One of the most striking findings is TM-?1's rapid and complete effect on NK cells. The antibody causes the immediate disappearance of NK1.1+ cells from peripheral blood within the first week of treatment. This effect is both profound and consistent across different study models.

CD8+ T Cell Modulation: While TM-?1 has a dramatic impact on NK cells, its effects on CD8+ T cells are more nuanced. The antibody causes a gradual reduction in massively expanded CD8+ T cell populations, though this process requires longer treatment periods compared to NK cell elimination. Importantly, certain subpopulations of CD8+ T cells, particularly long-term memory CD8+ T cells that co-express IL-15R? along with CD122 and CD132 subunits, show resistance to TM-?1 treatment.

Therapeutic Applications in Autoimmune Diseases

Type 1 Diabetes Prevention: TM-?1 has demonstrated significant efficacy in preventing diabetes development in NOD (Non-Obese Diabetic) mice, a primary animal model for Type 1 diabetes research. The antibody works by preferentially affecting major populations of islet-associated pathogenic cells, reducing their abundance and suppressing their differentiation into diabetogenic cells.

Celiac Disease-Like Pathology: In transgenic mice expressing human IL-15, TM-?1 treatment resulted in complete reversal of intestinal pathology resembling celiac disease. This included restoration of normal villus architecture, elimination of inflammatory cell infiltration in the lamina propria, and reversal of enterocyte damage.

Immunological Tolerance Restoration

A particularly important finding is that TM-?1 treatment appears to restore immunological tolerance through selective immune cell modulation. While the antibody significantly reduces pathogenic immune cell populations, regulatory T cells (Tregs) are only mildly affected by CD122 blockade. This selective preservation of regulatory mechanisms while eliminating pathogenic cells represents a promising therapeutic approach.

Histological and Functional Recovery

Treatment with TM-?1 has shown remarkable ability to reverse established pathological changes. In intestinal models, the antibody treatment led to complete restoration of normal tissue architecture, including reestablishment of proper villus-to-crypt height ratios and elimination of inflammatory infiltrates. This demonstrates that IL-15 blockade can not only prevent disease progression but also reverse established pathological changes.

Clinical Implications and Future Directions

The findings with TM-?1 suggest that IL-15 blockade represents a potentially powerful therapeutic strategy for treating autoimmune diseases. The antibody's ability to selectively target pathogenic immune cell populations while preserving regulatory mechanisms makes it an attractive candidate for clinical development. However, the resistance of certain memory T cell populations to treatment indicates that combination therapies or modified approaches may be necessary for complete therapeutic efficacy.

These research findings have established TM-?1 as an important tool for understanding IL-15-mediated immune responses and have provided strong preclinical evidence for the therapeutic potential of IL-15 blockade in autoimmune and inflammatory diseases.

Dosing regimens of clone TM-?1 in mouse models primarily vary by mouse strain and disease context, but standard protocols typically involve a single intraperitoneal injection at 5 mg/kg, especially in autoimmune models such as NOD mice.

• In NOD mice (a model for type 1 diabetes), TM-?1 is commonly administered as a single dose at 5 mg/kg intraperitoneally. This regimen is used to deplete CD122^+^ cells such as NK cells, with observation periods typically spanning 4 weeks to monitor cell depletion and recovery.

• In SCID mice (immunodeficient model), TM-?1 pretreatment has been used in protocols to enhance the survival of human cells post-engraftment. Specific dosing details in this context are not fully described, but the effect of TM-?1 treatment in combination with strain background is noted to significantly affect the experimental outcome.

Key points influencing regimen selection:

• Strain variability: The efficacy and kinetics of cell depletion with TM-?1 can vary by mouse strain. NOD mice display characteristic recovery kinetics of NK cells after TM-?1 injection, which may differ in other strains.
• Experimental context: Autoimmunity, engraftment studies, and other immunological models may affect the optimal timing and frequency. While a single-dose regimen is typical, protocols may be tailored based on the specific goals (e.g., sustained depletion vs. transient modulation).
• Comparison with engineered variants: Chimeric or Fc-silent clones such as ChMBC7, binding the same epitope and used at the same dose, may display altered pharmacodynamics (longer depletion, extended serum half-life) compared to TM-?1, suggesting that regimen could be adjusted for these variants.

Summary Table: TM-?1 Regimens in Mouse Models

For other diseases or mouse strains, dosing may require further adjustment based on the desired immunological effect, pharmacokinetics, and the unique properties of the mouse model. Always consult the specific literature and pilot dosing studies for optimal regimen design.