A ligand for OX40 (called OX40 ligand or OX40L) has been identified and has sequence similarity
to TNF. Mouse OX40L-immunoglobulin fusion protein (OX40L-Ig) binds to activated mouse CD4+ and CD8+ cells (1). OX40L is a type II membrane protein with significant identity to human gp34, a protein whose expression on HTLV-1- infected human leukemic T-cells is regulated by the tax gene (2). Modulation of the OX40–OX40L co-stimulatory interaction is a particularly promising therapeutic target for immunomodulation Of particular interest, inhibition of the OX40–OX40L co-stimulatory interaction has been shown to significantly reduce the incidence of autoimmune diabetes in NOD mice, a common animal model of type 1 diabetes. The OX40–OX40L interaction is a typical protein–protein interaction (PPI) (3).

1. Al-Shamkhani A. et al. OX40 is differentially expressed on activated rat and mouse T cells and is the sole receptor for the OX40 ligand. European Journal of Immunology. 1996 Aug, 26(8):1695-1699
2. Baum P.R. et al. Molecular characterization of murine and human OX40/OX40 ligand systems: identification of a human OX40 ligand as the HTLV-1-regulated protein gp34. The EMBO Journal. 1994 13(17):3992-4001
3. Song Y. et al. Small-molecule modulators of the OX40-OX40 ligand co-stimulatory protein-protein interaction. British Journal of Pharmacology. 2014 Jun 16, 171(21): 4955-4969