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

Clone TM-?1 is a well-characterized rat IgG2b monoclonal antibody that targets murine CD122 (IL-2/IL-15R?), and it is widely used in in vivo mouse studies to block interleukin-15 and interleukin-2 signaling by binding to the shared ? chain of their receptors.

In in vivo studies, TM-?1 is typically administered to mice via intraperitoneal (i.p.) injection. It is used at doses that are often in the range of 100 ?g per mouse per injection, but specific dosing regimens can vary depending on experimental goals. TM-?1 is employed to:

• Deplete or modulate CD122^+ cell populations, primarily affecting NK cells and memory CD8^+ T cells. In NOD mice, for instance, a single TM-?1 dose transiently depletes CD122^+ NK cells, with their partial recovery over several weeks.
• Suppress IL-15–driven pathology, such as autoimmune inflammation. In transgenic mouse models with IL-15–driven gut inflammation, repeated TM-?1 infusions (e.g., 16 infusions over 8 weeks) reverse tissue pathology, decrease lymphoid organ hypertrophy, and eliminate pathologic CD8^+ T cell subsets from the lamina propria.
• Prevent or modify disease progression in autoimmunity. TM-?1 has been used to suppress or prevent diabetes in the NOD model by impeding IL-2/IL-15 signaling, thus restoring immunological tolerance.
• Functional blockade in tumor immunology studies. TM-?1 enables the study of CD122’s role in antitumor immunity by ablating NK and memory CD8^+ T cell responses in mouse tumor models.

Experimental context and timing of administration are critical. TM-?1’s effect on cell populations is usually rapid but transient, and repeated dosing or combination with other antibodies (e.g., NK or T cell depleting clones) is sometimes required to maintain sustained blockade or cell depletion.

Summary of use:

• Purpose: Blockade of IL-2/IL-15 signaling via CD122
• Route: Commonly intraperitoneal injection
• Dosing: Varies; 100 ?g/mouse typical in some studies
• Effects: Depletes or functionally inactivates CD122^+ cells (e.g., NK cells, memory CD8^+ T cells); ameliorates autoimmune or inflammatory pathology; alters tumor immunity responses.

Caveats: Some CD8^+ memory T cells that coexpress additional receptor subunits may be less susceptible to depletion by TM-?1 due to receptor configuration, so not all CD122^+ populations are equivalently affected.

If you require details for a specific disease model, application, or dosing regimen, please clarify for a more tailored summary.

Sterile packaged clone TM-?1 (anti-mouse CD122/IL-2R? antibody) should be stored at 2–8°C (standard refrigerator temperature) for up to one month in its original, unopened, sterile packaging. For longer-term storage (beyond one month), it is recommended to aseptically aliquot the antibody into working volumes and store these aliquots at ? -70°C to ensure stability and prevent loss of function. Avoid repeated freeze-thaw cycles once aliquoted, as these can degrade the antibody.

Do not freeze the antibody in its original format until it is aliquoted for long-term storage. Always protect from light and avoid exposure to room temperature for extended periods, as is best practice for most monoclonal antibodies.

If you are using a product from another manufacturer, always check the specific product datasheet, but the above guidance is consistent across major suppliers for the TM-?1 clone.

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

TM-?1 is a monoclonal antibody that specifically targets the ? chain (CD122) shared by the IL-2 and IL-15 receptors. It is widely used in immunological research to study and modulate immune responses, especially in autoimmune and inflammatory disease models. Below are some of the other antibodies and proteins commonly used in combination with, or in the context of, TM-?1 in published research:

Anti-CD25 (IL-2R?) Antibodies

• Anti-CD25 (e.g., PC61 or similar clones): CD25 is the ? chain of the IL-2 receptor (IL-2R?). Since CD122 can pair with CD132 (?c) alone (forming an intermediate-affinity receptor) or with CD25 plus CD132 (forming the high-affinity receptor), blocking CD25 is often used to dissect IL-2 signaling from IL-15 signaling, as TM-?1 alone does not efficiently block the high-affinity IL-2 receptor complex.
• Rationale: These antibodies help to further distinguish the contributions of IL-2 versus IL-15 signaling pathways in immune regulation experiments.

Cytokines: IL-2 and IL-33

• Recombinant IL-2: Used to expand regulatory T cells (Tregs) and other IL-2-responsive populations. Studies have combined TM-?1 (anti-CD122) with IL-2 to investigate Treg expansion and function, especially in autoimmune diabetes models.
• Recombinant IL-33: IL-33 is an alarmin that signals through ST2 (IL-33R). In combination with anti-CD122, IL-33 has been shown to enhance Treg function and upregulate key markers (ICOS, KLRG1) associated with suppressive activity, particularly in tissue-resident Tregs, which express higher levels of ST2.
• Experimental Designs: Mice are often treated with TM-?1, then given daily injections of recombinant IL-2 or IL-33 to assess their combined effects on immune tolerance and Treg biology.

Flow Cytometry Markers for Immune Cell Subsets

• Anti-CD8, Anti-NK1.1, Anti-CD44: These antibodies are used to phenotype CD8+ T cells, NK cells, and memory/activated subsets, especially in experiments where TM-?1 is used to block IL-15 signaling and observe changes in these populations.
• Anti-CD132 (?c): The common gamma chain is a shared component of several cytokine receptors, including those for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. While TM-?1 targets CD122, antibodies against CD132 are used to further dissect receptor complex formation and signaling.
• Anti-ICOS, Anti-KLRG1: Used in studies assessing Treg function and phenotype after combined TM-?1 and cytokine treatments, as these markers are associated with Treg suppressive capacity.

Control Antibodies

• Isotype-matched control antibodies: Essential as negative controls in flow cytometry and functional assays to confirm specificity of TM-?1 effects.

Summary Table: Common Antibodies and Proteins Used with TM-?1

Key Findings from the Literature

• TM-?1 is often used with cytokines (IL-2, IL-33) to study Treg biology and immune tolerance, especially in autoimmune models like type 1 diabetes.
• Combining TM-?1 with anti-CD25 helps dissect the separate roles of IL-2 and IL-15 in immune regulation.
• Phenotyping antibodies (e.g., anti-CD8, anti-NK1.1, anti-CD44) are routinely used to assess the effects of TM-?1 on immune cell populations.
• IL-33, in particular, has been shown to enhance the suppressive function of Tregs when combined with CD122 blockade, highlighting tissue-specific effects.

These combinations and experimental designs are foundational in understanding the differential roles of IL-2 and IL-15 in immunity, and in developing targeted immunotherapies for autoimmune and inflammatory diseases.

Clone TM-?1 is a monoclonal antibody that targets the IL-2/IL-15 receptor beta chain (CD122) and has been extensively studied for its therapeutic potential in autoimmune diseases. The scientific literature reveals several important findings about this antibody's mechanisms and effects.

Mechanism of Action and Target Specificity

TM-?1 functions by binding to murine IL-2/IL-15R? (CD122), effectively blocking IL-15 signaling pathways. This blockade has profound effects on immune cell populations, particularly those that are highly dependent on IL-15 for survival and proliferation. The antibody demonstrates remarkable specificity in targeting IL-15-dependent cells while having minimal impact on other immune cell subsets.

Effects on Immune Cell Populations

NK Cell Elimination: One of the most striking findings is TM-?1's rapid and complete effect on natural killer (NK) cells. The antibody causes the immediate disappearance of NK1.1-positive cells from peripheral blood within the first week of treatment. This rapid depletion occurs because NK cells are exquisitely dependent on IL-15 for their survival and homeostasis.

CD8+ T Cell Modulation: The impact on CD8+ T cells is more nuanced and gradual. While TM-?1 treatment leads to a profound reduction in massively expanded CD8+ T cell populations, the effect requires longer treatment periods compared to NK cells. Importantly, the antibody appears to preferentially target activated or memory CD8+ T cells (CD44-high subset) while having limited effects on the total CD8+ T cell population in normal mice.

Therapeutic Efficacy in Autoimmune Models

Type 1 Diabetes Prevention: TM-?1 has demonstrated significant therapeutic potential in NOD (Non-Obese Diabetic) mice, a primary model for type 1 diabetes research. Treatment with anti-CD122 antibodies, including TM-?1, effectively suppressed diabetes development and prevented insulitis (pancreatic inflammation). The treatment resulted in markedly reduced severity of insulitis and fewer pancreas-infiltrated immune cells.

Intestinal Autoimmunity Reversal: In transgenic mice overexpressing human IL-15, TM-?1 treatment resulted in complete reversal of intestinal pathology. The antibody treatment restored normal intestinal architecture, including reestablishment of normal villus heights and elimination of lymphocytic infiltration in the lamina propria.

Histological and Pathological Improvements

The therapeutic effects of TM-?1 extend beyond cellular changes to include significant improvements in tissue pathology. In intestinal autoimmunity models, treatment reversed the entire spectrum of histologic changes, including massive lymphocytic infiltration, intraepithelial lymphocyte infiltration, and villus blunting. These improvements were comparable to those seen in non-transgenic control animals.

Treatment Resistance and Limitations

Despite its overall efficacy, TM-?1 treatment shows some limitations. A small subpopulation of CD8+CD44-high lymphocytes appears to be refractory to treatment, persisting even after extended therapy. This resistance may be attributed to certain memory CD8+ T cells that express the complete heterotrimeric IL-15 receptor complex, making them less susceptible to CD122-targeted blockade.

Clinical Translation Potential

The consistent findings across different autoimmune models suggest that TM-?1 and similar CD122-blocking antibodies represent a promising therapeutic approach. The mechanism appears to selectively target pathogenic immune cell populations while preserving essential immune functions, offering a more targeted approach to treating autoimmune diseases compared to broad immunosuppressive therapies.