Mouse B7-H2 (Fc-Fusion)

B7-H2, also called ICOS ligand, is a member of the co-stimulatory ligand family. B7-H2 interacts with its receptor, ICOS, on activated cell increases cytokine secretion and helper function to B cells. B7-H2 extracellular IgV domain interacts directly with ICOS, yet IgC domain is required for maintaining its structural integrity. M7096F contains both IgV and IgC domains of mouse B7-H2 and is fused with a mouse IgG2a Fc region.

Interacting protein(s): mouse ICOS
Related products: Checkpoint Proteins

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Description

Mouse ICOSL, also known as B7RP-1, was identified from a cDNA library prepared from activated intestinal intraepithelial lymphocytes (iIEL) via sequence comparison with B7.1 and B7.2 with 20% and 19% amino acid identity, respectively. While the homology is significant as the identity between B7.1 and B7.2 is only 24%. In addition the relative positions of 4 cysteine residues the overall length and the relative transmembrane domain of B7RP-1 are similar to those of B7 molecules. Expression of murine ICOSL is restricted to B cells and peritoneal macrophages.

Similar to B7.2, ICOSL stimulates T cell in vitro with a dose-dependent fashion in the presence of anti-CD3 antibody. ICOSL induces secretion of IFN-γ, but not IL-2 in co-stimulated T cells. In contrast, B7.2 induced both IFN-g and IL-2. In vivo, ICOSL-Fc protein exacerbates contact hypersensitivity, but notably when administered around the time of challenge than at the time of sensitization.

This observation is consistent with ICOSL’s role in co-stimulation of T cells but also indicates that the T cells better respond to ICOSL stimulation are those involved in the secondary immune response. Blockade of CD28-B7 or CD40-CD40L pathway inhibits contact hypersensitivity at the sensitization, but not the challenge, phase. Hence, ICOS-ICOSL pathway appears to be functionally distinct from other co-stimulatory pathways.

Amino Acid Sequence

References

1. Yang Q, Cao W, Wang Z, Zhang B, Liu J. Regulation of cancer immune escape: The roles of miRNAs in immune checkpoint proteins. Cancer Lett. 2018;431:73-84. Epub 20180522. doi: 10.1016/j.canlet.2018.05.015. PubMed PMID: 29800685.

2. Freeman GJ, Borriello F, Hodes RJ, Reiser H, Gribben JG, et al. (1993) Murine B7-2, an alternative CTLA4 counter-receptor that costimulates T cell proliferation and interleukin 2 production. J Exp Med. 178:2185-2192

3. Tang A, Judge TA, Turka LA. (1997) Blockade of CD40-CD40 ligand pathway induces tolerance in murine contact hypersensitivity. Eur J Immunol. 27:3143-3150.

4. Yoshinaga SK, Whoriskey JS, Khare SD, Sarmiento U, Guo J, et al. (1999) T-cell co-stimulation through B7RP-1 and ICOS. Nature. 402:827-832

5. Hutloff A, Dittrich AM, Beier KC, Eljaschewitsch B, Kraft R, Anagnostopoulos I, Kroczek RA. (1999) ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28. Nature. 397:263-266.