OX40 (Fc-Fusion)

The rat OX40 was originally identified as a surface molecule expressed on activated rat T lymphocyte that is recognized by a monoclonal antibody, MRC-OX-40. The identification of human ortholog was by the sequence homology of the cloned surface antigen recognized by a monoclonal antibody Ber-ACT35 on T blasts.

Interacting protein(s): OX40L
Related products: TNF-Receptor Superfamily

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Description

The rat OX40 was originally identified as a surface molecule expressed on activated rat T lymphocyte that is recognized by a monoclonal antibody, MRC-OX-40. The identification of human ortholog was by the sequence homology of the cloned surface antigen recognized by a monoclonal antibody Ber-ACT35 on T blasts. OX40 was since confirmed to be expressed primarily on activated CD4 T cells, some human T leukemia virus type I (HTLV-1)-infected T cell lines, but not on resting peripheral T cells, peripheral B cells or thymocytes. OX-40, along with other members TNF receptor superfamily, 4-1BB, CD27, CD30, and CD40 are co-stimulatory molecules plays a critical role in modulating immune responses.

Biologically, the OX40-OX40L axis has been shown to function relatively late in T cell activation as OX40L appears on APC a couple days after antigen was presented and OX40 only shows up on activated T cells. Deficiency of OX40-OX40L axis compromises the development of Th2, but not T1 cells. Structurally, complexes of OX40-OX40L revealed that the CRD1 of OX40 is also engaged in the interaction with OX40L. This is unusual as most other TNF receptor superfamily proteins utilize CRD2/CRD3 for engaging interaction with their ligands.

Similar to HVEM being the entry mediator for HSV, feline OX-40 was reported to be the mediator for feline immunodeficiency virus (FIV) suggesting human OX40 may facilitate infection of a yet identified virus.

Amino Acid Sequence.

References

1. Cebada J, Perez-Santos M, Bandala C, Lara-Padilla E, Herrera-Camacho I, Rosas-Murrieta NH, et al. OX40 agonists for cancer treatment: a patent review. Expert Opin Ther Pat. 2021;31(1):81-90. Epub 20201006. doi: 10.1080/13543776.2021.1825688. PubMed PMID: 32945223.

2. Antigens of activated rat T lymphocytes including a molecule of 50,000 Mr detected only on CD4 positive T blasts. Paterson DJ, Jefferies WA, Green JR, Brandon MR, Corthesy P, Puklavec M, Williams AF. Mol Immunol. 24:1281-90 (1987)

3. Characterization of the MRC OX40 antigen of activated CD4 positive T lymphocytes--a molecule related to nerve growth factor receptor. Mallett S, Fossum S, Barclay AN. EMBO J. 9:1063-8 (1990)

4. The human OX40 homolog: cDNA structure, expression and chromosomal assignment of the ACT35 antigen. Latza U., Duerkop H., Schnittger S., Ringeling J., Eitelbach F., Hummel M., Fonatsch C., Stein H. Eur. J. Immunol. 24:677-683 (1994)

5. Sustained survivin expression from OX40 costimulatory signals drives T cell clonal expansion. Song J, So T, Cheng M, Tang X, Croft M. Immunity. 22:621-31 (2005)