Human B- And T-Lymphocyte Attenuator (BTLA) Protein

Background

B and T Lymphocyte Attenuator (BTLA) is an immunoglobulin superfamily receptor expressed on various immune cells, notably B cells, T cells, macrophages, and dendritic cells. BTLA is a crucial immune checkpoint molecule that modulates immune responses by interacting with its ligand, Herpesvirus entry mediator (HVEM), to maintain immune homeostasis and prevent overactivation that could lead to autoimmune responses. As an immune checkpoint, BTLA is part of a larger family of inhibitory receptors, such as PD-1 and CTLA-4, that regulate immune cell activity to mitigate excessive inflammatory responses. However, BTLA has distinct binding affinities and structural features, which influence its role in modulating immune responses, inflammation, and tolerance. BTLA's interaction with HVEM is unique among immune checkpoint pathways because HVEM also binds several other ligands, including LIGHT (TNFSF14) and lymphotoxin α. This interaction allows for complex regulatory functions, enabling BTLA to provide inhibitory signals that dampen T cell receptor (TCR) and B cell receptor (BCR) signaling. Such regulation is vital in preventing autoimmunity and controlling immune responses in infection, inflammation, and cancer, where immune modulation can prevent tumor growth but also, if dysregulated, may suppress necessary immune responses against cancer cells.