CD258. also known as LIGHT (homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by T cells), is a member of the tumor necrosis factor (TNF) superfamily. It is encoded by the TNFSF14 gene and functions as a type II transmembrane protein, primarily expressed on immune cells such as activated T cells, dendritic cells, and natural killer cells. LIGHT interacts with two receptors: herpesvirus entry mediator (HVEM/TR2) and lymphotoxin β receptor (LTβR), as well as a soluble decoy receptor, decoy receptor 3 (DcR3), which modulates its activity. These interactions regulate immune responses, including T-cell activation, inflammation, and lymphoid tissue development.
CD258 antibodies target LIGHT and are studied for their therapeutic potential in immune-related diseases. In cancer, LIGHT promotes anti-tumor immunity by enhancing T-cell responses, making agonist antibodies a candidate for immunotherapy. Conversely, in autoimmune disorders (e.g., rheumatoid arthritis, inflammatory bowel disease), LIGHT overexpression contributes to pathological inflammation, prompting the development of neutralizing antibodies to block its pro-inflammatory signaling. CD258 antibodies are also explored in infectious diseases and transplant rejection. Preclinical studies highlight their dual role in either stimulating or dampening immune activity, depending on disease context. Ongoing research focuses on optimizing antibody specificity and delivery to balance efficacy with safety, positioning CD258 as a versatile target in immune modulation.