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

The Lymphocyte function-associated antigen 3 (LFA-3) – Cluster of differentiation 2 (CD2) interaction is a fundamental co-stimulatory and adhesion pathway essential for the human immune response [7, 11]. LFA-3 (also known as CD58) is a cell surface protein widely expressed on antigen-presenting cells (APCs), while its receptor, CD2, is primarily found on T cells and natural killer (NK) cells [10, 16]. The binding of LFA-3 to CD2 facilitates the formation and stabilization of the immunological synapse, providing a critical secondary signal for T-cell activation and proliferation [11, 19]. In chronic inflammatory conditions such as psoriasis, this pathway drives the activation of memory-effector T cells, which express high levels of CD2 [3, 4]. Therapeutic agents like alefacept, a recombinant LFA-3/IgG1 fusion protein, target this interaction by blocking the binding site and inducing the depletion of memory T cells through antibody-dependent cellular cytotoxicity (ADCC) [1, 8]. Clinical use of such agents requires monitoring of CD4+ T cell counts to prevent severe lymphopenia and minimize the risk of opportunistic infections [3, 12]. Beyond autoimmunity, the CD2-CD58 axis is increasingly recognized for its role in cancer immune evasion and as a potential target for enhancing anti-tumor immunity [7, 18].

Other names

CD58-CD2 interactionCD2-CD58 axisLFA3-CD2 pathwayCD2-LFA3 costimulatory pathway

Blocking the interaction between LFA-3 and CD2 to prevent T-cell co-stimulation and inducing apoptosis of memory T cells via antibody-dependent cellular cytotoxicity (ADCC).