Lymphocyte function-associated antigen 3 (CD58) and T-cell surface antigen CD2 interaction (LFA-3/CD2 interaction)

The interaction between Lymphocyte Function-Associated Antigen-3 (LFA-3, also known as CD58) and T-cell surface antigen CD2 is a fundamental costimulatory pathway in the human immune system (UniProt P19256, P06729). CD58 is a glycoprotein expressed on the surface of antigen-presenting cells (APCs), while CD2 is a receptor found on T cells and natural killer (NK) cells (News-Medical). Their binding facilitates cell-cell adhesion and provides a critical signal for T cell activation, proliferation, and the formation of the immunological synapse (NIH). This axis plays a significant role in the pathogenesis of autoimmune diseases like psoriasis and is also involved in transplant rejection and cancer immune evasion (Wikipedia, PNAS). Therapeutic strategies targeting this interaction focus on immunosuppression by blocking the costimulatory signal or depleting specific T cell subsets (Frontiers in Immunology). Alefacept, a fusion protein consisting of the CD2-binding portion of LFA-3 and a human IgG1 Fc domain, was the first biologic approved for treating moderate-to-severe plaque psoriasis (DrugBank). It works by preventing the LFA-3/CD2 interaction and inducing apoptosis in memory-effector T cells (Wikipedia). Other investigational agents, such as the anti-CD2 monoclonal antibody siplizumab, are being explored for use in organ transplantation and type 1 diabetes (Creative Biolabs, NIH). Clinical use of these therapies typically requires monitoring of CD4+ T cell counts to mitigate the risk of severe lymphopenia and opportunistic infections (Astellas Pharma).

Other names

CD58-CD2 interactionLFA-3/CD2 axisCD2-LFA-3 interactionT11/LFA-3 interactionErythrocyte rosette receptor interactionCD58-CD2 axis

Costimulatory blockade of T cell activation and selective depletion of memory T cells via antibody-dependent cellular cytotoxicity (ADCC)