CD58–CD2 costimulatory interface (CD58–CD2)

The CD58–CD2 costimulatory interface is a critical molecular interaction that facilitates adhesion and signal transduction between T lymphocytes and antigen-presenting cells (APCs). CD58, also known as Lymphocyte Function-Associated Antigen 3 (LFA-3), is a cell-surface glycoprotein expressed on APCs, while its ligand, CD2, is expressed on T cells and natural killer (NK) cells (UniProt P19235; UniProt P06729). The binding of CD58 to CD2 provides a potent costimulatory signal that works in tandem with the T cell receptor to promote T cell activation, proliferation, and cytokine production. In autoimmune diseases such as psoriasis, this pathway is exploited by pathogenic memory T cells to maintain chronic inflammation (Lebwohl et al., 2003, NEJM). Therapeutic agents like alefacept were developed to disrupt this interface, effectively reducing the activity and number of memory T cells. Furthermore, recent studies have identified the loss of CD58 as a key mechanism of immune evasion in various cancers, where its absence prevents effective T cell-mediated killing of tumor cells (Chua et al., 2024, Nature Communications). Understanding this interface is essential for developing therapies that either suppress unwanted immune responses or restore anti-tumor immunity.

Other names

LFA-3–CD2 interactionLymphocyte function-associated antigen 3–CD2 axisCD2–CD58 pathwayCD2–LFA-3 interface

The primary mechanism involves the competitive inhibition of the binding between CD58 (LFA-3) on antigen-presenting cells and CD2 on T cells. This blockade prevents the costimulatory signal required for T cell activation and proliferation. Additionally, fusion proteins like alefacept utilize an IgG1 Fc domain to induce the depletion of memory T cells through antibody-dependent cellular cytotoxicity (ADCC) by binding to FcγRIII receptors on natural killer cells (Lebwohl et al., 2003, NEJM; PubChem).