PDCD1LG2

Programmed cell death 1 ligand 2 (also known as PD-L2, B7-DC) is a protein that in humans is encoded by the PDCD1LG2 gene.^[5][6] PDCD1LG2 has also been designated as CD273 (cluster of differentiation 273). PDCD1LG2 is an immune checkpoint receptor ligand which plays a role in negative regulation of the adaptive immune response.^[5][7] PD-L2 is one of two known ligands for Programmed cell death protein 1 (PD-1).^[5]

Structure

PD-L2 is a

The crystal structure of murine PD-L2 bound to murine PD-1 has been determined.^[10] as well as the structure of the hPD-L2/mutant hPD-1 complex.^[11]

Expression

Profile

PD-L2 is primarily expressed on professional antigen presenting cells including dendritic cells (DCs) and macrophages.^[12] Others have shown PD-L2 expression in certain T helper cell subsets and cytotoxic T cells.^[13][14] PD-L2 protein is widely expressed in many healthy tissues including the GI tract tissues, skeletal muscles, tonsils, and pancreas.^[15] Additionally, PD-L2 has moderate to high expression in triple-negative breast cancer and gastric cancer and low expression in renal cell carcinoma.^[16] PD-L2 mRNA is widely expressed and not enriched in any particular tissue.^[15]

Regulation

Interleukin-4 (IL-4) and granulocyte-macrophage colony stimulating factor (GMCSF) both upregulate PD-L2 expression in DCs in vitro.^[12] IFN-α, IFN-β, and IFN-γ induce moderate upregulation of PD-L2 expression.^[12]

Function

PD-L2 binds to its receptor PD-1 with

PD-L2, PD-L1, and PD-1 expressions are important in the immune response to certain cancers. Due to their role in suppressing the adaptive immune system, efforts have been made to block PD-1 and PD-L1, resulting in FDA approved inhibitors for both (see pembrolizumab, nivolumab, atezolizumab). There are still no FDA approved inhibitors for PD-L2 as of 2019.^[19]

The direct role of PD-L2 in cancer progression and immune-tumor microenvironment regulation is not as well studied as the role of PD-L1.^[16] In mouse cell cultures, PD-L2 expression on tumor cells suppressed cytotoxic T cell-mediated immune responses.^[20]

Indirectly, PD-L2 may have utility as a

Further reading

• Tseng SY, Otsuji M, Gorski K, Huang X, Slansky JE, Pai SI, et al. (April 2001). "B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells". The Journal of Experimental Medicine. 193 (7): 839–46.
  PMID 11283156
  .
• Brown JA, Dorfman DM, Ma FR, Sullivan EL, Munoz O, Wood CR, et al. (February 2003). "Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production". Journal of Immunology. 170 (3): 1257–66.
  PMID 12538684
  .
• Youngnak P, Kozono Y, Kozono H, Iwai H, Otsuki N, Jin H, et al. (August 2003). "Differential binding properties of B7-H1 and B7-DC to programmed death-1". Biochemical and Biophysical Research Communications. 307 (3): 672–7.
  PMID 12893276
  .
• Tsushima F, Iwai H, Otsuki N, Abe M, Hirose S, Yamazaki T, et al. (October 2003). "Preferential contribution of B7-H1 to programmed death-1-mediated regulation of hapten-specific allergic inflammatory responses". European Journal of Immunology. 33 (10): 2773–82.
  S2CID 34992725
  .
• Aramaki O, Shirasugi N, Takayama T, Shimazu M, Kitajima M, Ikeda Y, et al. (January 2004). "Programmed death-1-programmed death-L1 interaction is essential for induction of regulatory cells by intratracheal delivery of alloantigen". Transplantation. 77 (1): 6–12.
  S2CID 25360886
  .
• He XH, Liu Y, Xu LH, Zeng YY (April 2004). "Cloning and identification of two novel splice variants of human PD-L2". Acta Biochimica et Biophysica Sinica. 36 (4): 284–9.
  PMID 15253154
  .
• Zhang Z, Henzel WJ (October 2004). "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Science. 13 (10): 2819–24.
  PMID 15340161
  .
• Ohigashi Y, Sho M, Yamada Y, Tsurui Y, Hamada K, Ikeda N, et al. (April 2005). "Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer". Clinical Cancer Research. 11 (8): 2947–53.
  PMID 15837746
  .
• Saunders PA, Hendrycks VR, Lidinsky WA, Woods ML (December 2005). "PD-L2:PD-1 involvement in T cell proliferation, cytokine production, and integrin-mediated adhesion". European Journal of Immunology. 35 (12): 3561–9.
  S2CID 43876326
  .
• Pfistershammer K, Klauser C, Pickl WF, Stöckl J, Leitner J, Zlabinger G, et al. (May 2006). "No evidence for dualism in function and receptors: PD-L2/B7-DC is an inhibitory regulator of human T cell activation". European Journal of Immunology. 36 (5): 1104–13.
  PMID 16598819
  .
• Abelson AK, Johansson CM, Kozyrev SV, Kristjansdottir H, Gunnarsson I, Svenungsson E, et al. (January 2007). "No evidence of association between genetic variants of the PDCD1 ligands and SLE". Genes and Immunity. 8 (1): 69–74.
  PMID 17136123
  .
• Mataki N, Kikuchi K, Kawai T, Higashiyama M, Okada Y, Kurihara C, et al. (February 2007). "Expression of PD-1, PD-L1, and PD-L2 in the liver in autoimmune liver diseases". The American Journal of Gastroenterology. 102 (2): 302–12.
  S2CID 8083797
  .
• Wang SC, Lin CH, Ou TT, Wu CC, Tsai WC, Hu CJ, et al. (April 2007). "Ligands for programmed cell death 1 gene in patients with systemic lupus erythematosus". The Journal of Rheumatology. 34 (4): 721–5.
  PMID 17343323
  .

External links

• PDCD1LG2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This membrane protein–related article is a stub. You can help Wikipedia by expanding it.

• v
• t
• e