Lymphocyte function-associated antigen 3 (LFA-3) (LFA-3)

Lymphocyte function-associated antigen 3 (LFA-3), also designated as CD58, is a cell surface glycosylated protein and a member of the immunoglobulin superfamily (Source: UniProt P19235). It is constitutively expressed on a wide variety of cells, most notably antigen-presenting cells (APCs), endothelial cells, and erythrocytes (Source: PubMed: 2461245). LFA-3 serves as the primary adhesion and costimulatory ligand for the CD2 receptor, which is found on the surface of T lymphocytes and natural killer (NK) cells (Source: NCBI Gene: 965). The LFA-3/CD2 interaction is critical for stabilizing the immunological synapse and enhancing T-cell receptor-mediated signaling, which drives T-cell activation and the subsequent immune response (Source: StatPearls, Psoriasis). In clinical practice, this pathway has been targeted by the fusion protein alefacept to treat chronic plaque psoriasis by selectively depleting memory T cells. Beyond autoimmune applications, the loss or downregulation of LFA-3 on certain tumor cells is recognized as a mechanism of immune evasion, as it impairs the ability of T cells to recognize and eliminate malignant cells (Source: PubMed: 28972054).

Other names

CD58Surface glycoprotein LFA-3Ag3Lymphocyte function-associated antigen 3

Alefacept is a recombinant fusion protein consisting of the extracellular CD2-binding domain of human LFA-3 linked to the Fc portion of human IgG1. It acts by binding to the CD2 receptor on T lymphocytes, thereby competitively inhibiting the interaction between endogenous LFA-3 on antigen-presenting cells and CD2 on T cells. This blockade prevents T-cell activation and proliferation. Furthermore, the Fc portion of alefacept binds to Fc-gamma-RIII receptors on natural killer cells, triggering the targeted apoptosis of memory-effector T cells (Source: DrugBank DB00024; PubMed: 12452868).