Lymphocyte function-associated antigen 3 (CD58) (LFA-3)

Lymphocyte function-associated antigen 3 (LFA-3), also known as CD58, is a cell surface glycosylated protein belonging to the immunoglobulin superfamily [1, 5]. It is widely expressed on various cell types, including antigen-presenting cells (APCs), endothelial cells, and erythrocytes [1]. LFA-3 serves as the primary ligand for the CD2 receptor, which is predominantly expressed on T lymphocytes and natural killer (NK) cells [2]. The interaction between LFA-3 and CD2 is critical for mediating adhesion between T cells and APCs, thereby facilitating the formation of the immunological synapse [4]. Beyond simple adhesion, this interaction provides a potent costimulatory signal that enhances T-cell activation, proliferation, and cytokine production [5]. In pathological states such as chronic plaque psoriasis, the LFA-3/CD2 pathway is overactive, leading to the sustained activation of memory-effector T cells [4]. Therapeutic intervention, most notably with the fusion protein Alefacept, targets this pathway by blocking the LFA-3/CD2 binding site and inducing the selective depletion of memory T cells through Fc-mediated mechanisms [3].

Other names

CD58Ag3Surface glycoprotein LFA-3LFA3

Alefacept is a recombinant human fusion protein that consists of the extracellular CD2-binding portion of LFA-3 linked to the Fc portion of human IgG1 [3]. It works by binding to CD2 on T cells, thereby blocking the interaction between LFA-3 and CD2, which inhibits T-cell activation and proliferation [4]. Additionally, the Fc portion of the molecule interacts with FcγRIII on NK cells to induce apoptosis of memory-effector T cells via antibody-dependent cellular cytotoxicity (ADCC) [3].