Engagement of CD28 by B7-1 (CD80) or B7-2 (CD86) in the presence of antigen promotes T cell proliferation, cytokine production, differentiation of effector T cells, and the induction of Bcl-x, a promoter of T cell survival. Conversely, engagement of CTLA4 by B7-1 or B7-2 may inhibit proliferation and IL-2 production. Pdcd-1L1 (programmed cell death ligand-1), also known as B7-H1 or PD-L1, is 290 amino acid type I transmembrane protein which is 20% and 15% identical to B7-1 and B7-2, respectively. Pdcd-1L2 has immunoglobulin V-like and C-like domains and a 30 amino acid cytoplasmic tail. It does not bind CD28, cytotoxic T-lymphocyte A4 or ICOS (inducible co-stimulator). IL-2, although produced in small amounts, is required for the effect of Pdcd-1L1 co-stimulation. The gene which encodes Pdcd-1L1 maps to human chromosome 9p24. Pdcd-1L2 (programmed cell death ligand-2) is a 73 amino acid protein which contains a signal sequence, IgV- and IgC-like domains, a transmembrane region and a cytoplasmic region. The gene which encodes Pdcd-1L2 maps to human chromosome 9p24.2. The constitutive expression of Pdcd-1L1 and Pdcd-1L2 on paren-chymal cells of heart, lung and kidney suggests that the Pdcd-1-Pdcd-L system could provide unique negative signaling to help prevent autoimmune disease.
背景文献
1. Jurado J.O., et al. 2008. Programmed death (PD)-1:PD-ligand 1/PD-ligand 2 pathway inhibits T cell effector functions during human tuberculosis. J. Immunol. 181:116-125.
2. Boorjian S.A., et al. 2008. T-cell coregulatory molecule expression in urothelial cell carcinoma: clinicopathologic correlations and association with survival. Clin. Cancer Res. 14:4800-4808.
序列相似性
Belongs to the immunoglobulin superfamily. BTN/MOG family.
组织特异性
Highly expressed in the heart, skeletal muscle, placenta and lung. Weakly expressed in the thymus, spleen, kidney and liver. Expressed on activated T- and B-cells, dendritic cells, keratinocytes and monocytes.
翻译后修饰
Ubiquitinated; STUB1 likely mediates polyubiquitination of PD-L1/CD274 triggering its degradation.
亚细胞定位
Cell membrane, Early endosome membrane, Recycling endosome membrane, Nucleus.
Western blot analysis of PD-L1 on different lysates with Rabbit anti-PD-L1 antibody (ET1701-41) at 1/5,000 dilution.
Lane 1: MDA-MB-231 cell lysate Lane 2: A375 cell lysate Lane 3: U-87 MG cell lysate Lane 4: THP-1 cell lysate
Lysates/proteins at 20 µg/Lane.
Predicted band size: 33 kDa Observed band size: 45 kDa
Exposure time: 3 minutes 10 seconds;
4-20% SDS-PAGE gel.
Proteins were transferred to a PVDF membrane and blocked with 5% NFDM/TBST for 1 hour at room temperature. The primary antibody (ET1701-41) at 1/5,000 dilution was used in 5% NFDM/TBST at 4℃ overnight. Goat Anti-Rabbit IgG - HRP Secondary Antibody (HA1001) at 1:50,000 dilution was used for 1 hour at room temperature.
Immunohistochemical analysis of paraffin-embedded human non-small cell lung cancer tissue using anti-PD-L1 antibody. The section was pre-treated using heat mediated antigen retrieval with Tris-EDTA buffer (pH 8.0-8.4) for 20 minutes.The tissues were blocked in 5% BSA for 30 minutes at room temperature, washed with ddH2O and PBS, and then probed with the primary antibody (ET1701-41, 1/200) for 30 minutes at room temperature. The detection was performed using an HRP conjugated compact polymer system. DAB was used as the chromogen. Tissues were counterstained with hematoxylin and mounted with DPX.
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