Anti-Mouse CD137L (4-1BBL) – Purified in vivo GOLD™ Functional Grade

Common In Vivo Applications of Clone TKS-1 in Mice

Clone TKS-1 is a monoclonal antibody specific for mouse 4-1BB ligand (4-1BBL, also known as CD137L), a molecule critical for T cell co-stimulation in immune responses. Its in vivo use in mouse models is primarily focused on manipulating immune system signaling for research purposes.

Mechanism of Action

• Blockade of 4-1BB/4-1BBL Interaction: TKS-1 binds to mouse 4-1BBL, preventing its interaction with 4-1BB (CD137) on T cells. This blockade disrupts the co-stimulatory signal that normally enhances T cell proliferation, survival, and cytokine production, particularly during immune responses.
• Functional Consequences: By inhibiting this pathway, TKS-1 can attenuate T cell activation and expansion, which is especially relevant in contexts where augmented or dysregulated T cell responses are undesirable.

Typical In Vivo Applications

• Immune Response Modulation: TKS-1 is used to study the role of 4-1BBL in T cell-dependent immune responses, such as during infection, autoimmunity, or transplantation. By blocking 4-1BBL, researchers can assess the contribution of this pathway to immune activation or tolerance.
• Cancer Immunotherapy Research: Since the 4-1BB/4-1BBL axis is important for antitumor immunity—particularly in enhancing CD8+ T cell responses—TKS-1 is employed to investigate how disrupting this pathway affects tumor growth and the efficacy of immunotherapies. For example, it can be used to determine whether blocking 4-1BBL diminishes the antitumor effects of therapies that rely on T cell activation.
• Modeling Immune Regulation: TKS-1 is useful for creating models of immune suppression or to test the specificity of other immunomodulatory agents. Its ability to block T cell proliferation and cytokine production when co-stimulated via 4-1BBL makes it a tool for dissecting complex immune interactions in vivo.

Experimental Evidence

• Specificity and Efficacy: TKS-1 has been shown to block the binding of soluble 4-1BB to 4-1BBL-expressing cells in vitro, confirming its specificity and functional activity.
• In Vivo Validation: While most available information emphasizes in vitro and mechanistic studies, the antibody is marketed and used for in vivo applications in mice, particularly where precise modulation of the 4-1BB/4-1BBL interaction is required.

Summary Table

Conclusion

Clone TKS-1 is predominantly used in vivo in mice to block the 4-1BB/4-1BBL co-stimulatory pathway, thereby modulating T cell responses in the contexts of immunity, cancer, and immune regulation. Its application helps clarify the role of this pathway in health and disease and supports the development of targeted immunotherapies.

Commonly used antibodies or proteins paired with TKS-1 (anti-mouse 4-1BBL/CD137L) in the literature include:

• 3H3 (anti-4-1BB/CD137 antibody): Frequently used alongside TKS-1 to investigate the 4-1BB/4-1BBL signaling pathway in immunological studies, especially in T cell co-stimulation and blocking studies.
• Anti-CD3: Used in co-stimulation assays to trigger T cells, enabling the study of how TKS-1 influences T cell proliferation and cytokine production in response to 4-1BBL engagement.
• Clone 19H3: Another monoclonal antibody against mouse 4-1BBL that is sometimes directly compared or used in conjunction with TKS-1 to assess binding sites or block the 4-1BBL/4-1BB interaction.
• Thy1.1 (CD90.1): An antibody used for tracking adoptively transferred T cells (such as pmel-1 Thy1.1+ CD8+ T cells) in experiments analyzing how TKS-1 treatment affects T cell behavior.
• CFSE (Carboxyfluorescein succinimidyl ester): A fluorescent dye, not a protein or antibody, but commonly used with TKS-1 in proliferation and tracking assays for transferred cells in in vivo studies.

Key applications for these antibody combinations include:

• Blocking studies: TKS-1 blocks the interaction between 4-1BBL and 4-1BB, so is often used together with stimulatory anti-4-1BB antibodies (such as 3H3) to dissect pathway roles.
• Functional assays: In co-stimulation, anti-CD3 is used with TKS-1 and 4-1BBL-expressing cells to study T cell activation, proliferation, and cytokine secretion.
• Combination therapy models: Research sometimes combines agonistic and antagonistic antibodies (e.g., 3H3 with TKS-1) to study effects on tumor growth or immune cell function.

In summary, 3H3 (anti-4-1BB) and anti-CD3 are the most commonly cited antibodies used together with TKS-1 in immune regulation and functional studies of the 4-1BB/4-1BBL axis. 19H3 is also used for comparative binding studies.

Clone TKS-1 is a monoclonal antibody widely used in immunological research for its specificity to mouse 4-1BB Ligand (4-1BBL/CD137L), and scientific literature consistently reports several key findings:

• Specificity and Blocking Function: TKS-1 is highly specific for murine 4-1BBL, binding robustly to cells expressing the molecule (e.g., 4-1BBL-transfected L5178Y, NRK, and P815 cells). Pre-incubation with TKS-1 effectively blocks 4-1BB–Ig binding to 4-1BBL-expressing cells, demonstrating its utility for interrupting the interaction between 4-1BBL and its receptor, 4-1BB (CD137), making it valuable for mechanistic and blocking studies in vivo and in vitro.

• Agonistic Signaling: Compared to stronger agonist clones like 3H3, TKS-1 induces only mild agonistic signaling of 4-1BB, meaning it does not robustly activate downstream signaling through 4-1BB, but is more useful for blocking rather than activation.

• Functional Studies and Immunomodulation: By blocking 4-1BBL, TKS-1 can inhibit the co-stimulatory effect that 4-1BBL has on T cells, including the proliferation and cytokine production normally triggered when T cells interact with antigen-presenting cells expressing 4-1BBL.

• Epitope Recognition: TKS-1 binds to an epitope overlapping the 4-1BB binding site on 4-1BBL. This epitope specificity is distinct from some other anti-4-1BBL clones, allowing for studies of ligand-receptor interactions and of site-specific blocking.

• Expression Studies: TKS-1 has been reported and validated for flow cytometric analysis to detect 4-1BBL expression on activated antigen-presenting cells (e.g., B cells, macrophages, dendritic cells), making it widely used in basic immunology research.

Summary of utility:
TKS-1 is primarily valued in the literature for its blocking activity, high specificity, and distinct agonistic profile—it disrupts 4-1BB/4-1BBL interactions without triggering strong activating signals, and thus is particularly useful for dissecting the role of 4-1BBL-mediated costimulation in murine immune models.

There are no published dosing regimens specific for the clone TKS-1 antibody in mice, and detailed comparisons across different mouse models are not available in the current literature.

Clone TKS-1 is a monoclonal antibody that specifically binds to mouse 4-1BBL (CD137L), blocking its interaction with the receptor 4-1BB and thereby used for inhibitory studies in immunological research. While its binding characteristics and functional effects have been described, the optimal dosing schedule, route, and frequency for TKS-1 in various mouse models (such as different strains, disease models, or immune states) remain unreported in peer-reviewed sources.

Essential context and supporting details:

• Experimental use of TKS-1 is primarily characterized by its specificity and competitive binding to the receptor site of 4-1BBL, making it a valuable reagent for functional blockade studies rather than for direct dosing regimen development.
• In the broader context of monoclonal antibody dosing in mice, typical administration regimens (for other antibodies) often include doses ranging from 1 to 10 mg/kg given as single or repeated injections, but these are not directly translatable to TKS-1 without specific experimental validation.
• Researchers planning TKS-1 dosing experiments generally need to conduct pilot studies to empirically determine effective dosing based on the specific model, endpoints, and desired functional blockade, potentially starting with doses and schedules established for similar monoclonal antibodies.

In summary, no standardized or published dosing regimens for clone TKS-1 are available for any mouse model; all experimental protocols must be empirically developed.