Butyrophilin subfamily 3 member A1 (CD277) (CD277)

CD277, primarily represented by the isoform Butyrophilin subfamily 3 member A1 (BTN3A1), is a type I transmembrane protein belonging to the butyrophilin family and the immunoglobulin superfamily [8, 12]. It is a member of the B7-like family of costimulatory molecules and is widely expressed on various immune and non-immune cells [1, 14]. CD277 plays a pivotal role in the activation of Vgamma9Vdelta2 T cells, a major subset of human gamma-delta T cells, by acting as a sensor for intracellular phosphoantigens (PAgs) such as isopentenyl pyrophosphate (IPP) [11]. These PAgs accumulate in cells during metabolic stress, bacterial infection, or oncogenic transformation and bind to the intracellular B30.2 domain of BTN3A1, inducing a conformational change in the extracellular domain that is recognized by the gamma-delta T-cell receptor [8, 11]. This interaction triggers the activation, proliferation, and cytotoxic activity of gamma-delta T cells, enabling them to identify and eliminate stressed or cancerous cells [8, 11]. In various cancers, including ovarian and acute myeloid leukemia, CD277 can also act as a negative co-stimulatory molecule that contributes to immunosuppression and tumor evasion [1, 2, 5]. Therapeutic antibodies such as ICT01 are being developed to agonize CD277, thereby bypassing the need for phosphoantigen accumulation to potently activate gamma-delta T cells for anti-tumor therapy [5, 10].

Other names

BTN3A1BTN3AButyrophilin 3A1BTF5BT3.1CD277

Agonism of CD277 (BTN3A1) to induce a conformational change in the extracellular domain that mimics phosphoantigen-induced activation of Vgamma9Vdelta2 T cells, leading to targeted lysis of tumor cells; Blockade of CD277 to prevent inhibitory co-stimulation of alpha-beta T cells in the tumor microenvironment.