The TKS-1 monoclonal antibody reacts with mouse 4-1BB ligand (4-1BBL), a type II transmembrane glycoprotein also known as CD137L. 4-1BBL is a 97 kDa member of the TNF superfamily and is expressed by dendritic cells, macrophages, and activated B and T lymphocytes. Interaction of 4-1BBL with 4-1BB (CD137) provides costimulatory signals to both CD4 and CD8 T cells through the activation of NF-κB, c-Jun and p38 downstream pathways. The TKS-1 antibody has been shown to inhibit the binding of soluble 4-1BB to 4-1BBL in vitro.

InVivoMAb anti-mouse 4-1BBL (CD137L) (Clone: TKS-1)

Welten, S. P., et al. (2015). “The viral context instructs the redundancy of costimulatory pathways in driving CD8(+) T cell expansion.” Elife 4. PubMed

Signals delivered by costimulatory molecules are implicated in driving T cell expansion. The requirements for these signals, however, vary from dispensable to essential in different infections. We examined the underlying mechanisms of this differential T cell costimulation dependence and found that the viral context determined the dependence on CD28/B7-mediated costimulation for expansion of naive and memory CD8(+) T cells, indicating that the requirement for costimulatory signals is not imprinted. Notably, related to the high-level costimulatory molecule expression induced by lymphocytic choriomeningitis virus (LCMV), CD28/B7-mediated costimulation was dispensable for accumulation of LCMV-specific CD8(+) T cells because of redundancy with the costimulatory pathways induced by TNF receptor family members (i.e., CD27, OX40, and 4-1BB). Type I IFN signaling in viral-specific CD8(+) T cells is slightly redundant with costimulatory signals. These results highlight that pathogen-specific conditions differentially and uniquely dictate the utilization of costimulatory pathways allowing shaping of effector and memory antigen-specific CD8(+) T cell responses.

 

Kurche, J. S., et al. (2010). “Comparison of OX40 ligand and CD70 in the promotion of CD4+ T cell responses.” J Immunol 185(4): 2106-2115. PubMed

The TNF superfamily members CD70 and OX40 ligand (OX40L) were reported to be important for CD4(+) T cell expansion and differentiation. However, the relative contribution of these costimulatory signals in driving CD4(+) T cell responses has not been addressed. In this study, we found that OX40L is a more important determinant than CD70 of the primary CD4(+) T cell response to multiple immunization regimens. Despite the ability of a combined TLR and CD40 agonist (TLR/CD40) stimulus to provoke appreciable expression of CD70 and OX40L on CD8(+) dendritic cells, resulting CD4(+) T cell responses were substantially reduced by Ab blockade of OX40L and, to a lesser degree, CD70. In contrast, the CD8(+) T cell responses to combined TLR/CD40 immunization were exclusively dependent on CD70. These requirements for CD4(+) and CD8(+) T cell activation were not limited to the use of combined TLR/CD40 immunization, because vaccinia virus challenge elicited primarily OX40L-dependent CD4 responses and exclusively CD70-dependent CD8(+) T cell responses. Attenuation of CD4(+) T cell priming induced by OX40L blockade was independent of signaling through the IL-12R, but it was reduced further by coblockade of CD70. Thus, costimulation by CD70 or OX40L seems to be necessary for primary CD4(+) T cell responses to multiple forms of immunization, and each may make independent contributions to CD4(+) T cell priming.