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CD272, also known as B- and T-lymphocyte attenuator (BTLA), is an inhibitory receptor belonging to the CD28 immunoglobulin superfamily. It is encoded by the BTLA gene and primarily expressed on B cells, T cells, macrophages, and dendritic cells. BTLA plays a crucial role in regulating immune responses by acting as a negative regulator of antigen receptor signaling. Its ligand is HVEM (herpesvirus entry mediator, also known as CD270), and their interaction inhibits T cell and B cell activation, proliferation, and cytokine production. Structurally, BTLA is similar to other immune checkpoint proteins like PD-1 and CTLA-4, containing an extracellular IgV-like domain and intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that mediate its inhibitory functions. BTLA's signaling involves the recruitment of tyrosine phosphatases SHP-1 and SHP-2, which dampen immune activation. Due to its role in immune regulation, the BTLA-HVEM axis is considered a promising target for cancer immunotherapy.