Lymphocyte function-associated antigen 3 (LFA-3) – Cluster of differentiation 2 (CD2) complex (LFA-3 – CD2 complex)

The Lymphocyte function-associated antigen 3 (LFA-3) – Cluster of differentiation 2 (CD2) complex is a critical mediator of the immune response, formed by the interaction between LFA-3 (also known as CD58) and its receptor, CD2 (UniProt: P19235, P06729). LFA-3 is widely expressed on the surface of antigen-presenting cells, endothelial cells, and epithelial cells, while CD2 is primarily found on T lymphocytes and natural killer (NK) cells (PubMed: 10438934). This interaction facilitates stable cell-cell adhesion and provides essential costimulatory signals that lower the threshold for T cell receptor (TCR) activation, promoting T cell proliferation and cytokine production (PubMed: 1633953). In autoimmune and inflammatory conditions, such as chronic plaque psoriasis, this pathway is overactive, leading to the sustained activation of memory-effector T cells (StatPearls: NBK548582). Therapeutic targeting of this complex, most notably with the fusion protein alefacept, aims to disrupt this costimulatory signal and selectively deplete the pathogenic memory T cell population (DrugBank: DB00028). By binding to CD2, these therapies can effectively reduce inflammatory symptoms while maintaining a degree of overall immune competence compared to broader immunosuppressants.

Other names

CD58-CD2 complexLFA3-CD2 interactionCD58-CD2 adhesion pathwayLymphocyte function-associated antigen 3 – Cluster of differentiation 2 interaction

Alefacept, a fusion protein consisting of the extracellular CD2-binding portion of LFA-3 linked to the Fc portion of human IgG1, binds to CD2 on T cells (DrugBank: DB00028). This action blocks the interaction between LFA-3 and CD2, thereby inhibiting T cell activation and proliferation. Additionally, the Fc portion of the drug interacts with FcγRIII (CD16) on NK cells to induce apoptosis of memory-effector T cells (CD45RO+), which are the primary drivers of chronic plaque psoriasis (PubMed: 12648212).