Butyrophilin family protein (BTN)

The Butyrophilin (BTN) family proteins are a group of type I transmembrane glycoproteins belonging to the immunoglobulin (Ig) superfamily, structurally similar to the B7 family of costimulatory molecules (Arnett, H. A., & Viney, J. L., 2014, Nature Reviews Immunology). These proteins are pivotal regulators of the immune system, specifically acting as essential mediators for the activation of gamma-delta (γδ) T cells. For instance, the BTN3A1 and BTN2A1 subunits form a complex that senses intracellular phosphoantigens, which are often elevated in cancer cells or during infections, thereby triggering a rapid T cell-mediated immune response (Rigau, M., et al., 2020, Science). Beyond immune modulation, some members like BTN1A1 are involved in the secretion of milk fat globules in the mammary gland (UniProt, P35901). In the context of drug development, the BTN family is viewed as a promising class of next-generation immune checkpoints. Therapeutic candidates such as ICT01 are designed to bind BTN3A, mimicking the effect of phosphoantigens to selectively activate γδ T cells for the treatment of solid and hematologic tumors (ImCheck Therapeutics, 2024).

Other names

ButyrophilinButyrophilin-like proteinBTNLB7-like protein

Agonistic monoclonal antibodies targeting BTN3A isoforms to induce a conformational change that facilitates the activation of Vγ9Vδ2 T cells against tumor cells.