PD-1 contains a single extracellular IgV domain. Engagement of PD-1 with its ligand (PD-L1 or PD-L2) triggers inhibitory signalling which is considered as a hallmark of failed antitumor immunity. P099G contains the human PD-1 ECD fused with an aglycosylated mouse IgG2a Fc domain.
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|Synonym:||CD279, PDCD1, (programmed cell death 1), hPD-1, hPD-l, PD1, SLEB2|
|Tag:||Aglycosylated mouse IgG2a-Fc|
|MW (Calculated):||39,663 daltons|
|MW (SDS-PAGE):||42 Kd|
|Abs 0.1% (= 1 mg/ml):||1.047|
PD-1 was identified in apoptosis induced cells by subtractive hybridization. Like other CD28, CTLA-4 and ICOS, it is a membrane anchored IgSF family member and like CTLA-4, it contains a single IgV excellular domain and an ITIM (immune receptor tyrosine based inhibition motif)-containing intracellular region. PD-1 lacks the MYPPPY motif that is required for binding of B7-1 and B7-2, instead it binds to two ligands, PDL1 and PDL2.
The major function of PD-1 is to limit T cell activity during an inflammatory response to infection and to limit autoimmunity. In this capacity, PD-1 regulates effector T cell activity and plays a critical role in resistance of tumor cells to immune surveillance. In contrast, CTLA-4 functions as a signal dampener for T cell activation. Engagement of PD-1 with its ligand (PD-L1 and PD-L2) triggers inhibitory signal, diminish cell proliferation and cytokine production. The PD-1/PDL1/PDL2 axis is therefore widely demonstrated to contribute to failed antitumor immunity. PD-1 deficiency, similar to CTLA-4 deficiency, results in lymphoproliferative disorders including splenomegaly, B cell expansion, with elevated serum antibody levels, lupus glomerulonephritis, arthritis, and autoimmune cardiomyopathy. Thus, after T cell activation, PD-1 and CTLA-4 are upregulated in order to contain the T cell response. Both molecules appear to be critical for maintenance of tolerance, though PD-1 appears to be more important for the peripheral than central tolerance.
On the non-professional antigen presenting parenchymal cells (do not express B7-1 and B7-1), the expression of PD-1 ligands and the B7-H2 (ICOS ligand) underlying the counter-balance nature of the PD-1 and ICOS pathways.
Amino Acid Sequence
- Structure and chromosomal localization of the human PD-1 gene (PDCD1). Shinohara T., Taniwaki M., Ishida Y., Kawaich M., Honjo T. Genomics 23:704-706 (1994)
- The role of the PD-1 pathway in autoimmunity and peripheral tolerance. Fife B.T., Pauken K.E. Ann. N. Y. Acad. Sci. 1217:45-59 (2011)
- Role of the PD-1 pathway in the immune response. Riella L.V., Paterson A.M., Sharpe A.H., Chandraker A. Am. J. Transplant. 12:2575-87 (2012)