Cluster of Differentiation 4 (CD4) is also known as T-cell surface antigen T4/Leu-3 (LEU-3) and CD4mut, is a single-pass type I membrane glycoprotein,and is a member of the immunoglobulin superfamily. CD4 expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It has four immunoglobulin domains (D1 to D4) that are exposed on the extracellular surface of the cell: D1 and D3 resemble immunoglobulin variable (IgV) domains. D2 and D4 resemble immunoglobulin constant (IgC) domains. CD4 is a co-receptor that assists the T cell receptor (TCR) with an antigen-presenting cell. Using its portion that resides inside the T cell, CD4 amplifies the signal generated by the TCR by recruiting an enzyme, known as the tyrosine kinase lck, which is essential for activating many molecules involved in the signaling cascade of an activated T cell. CD4 also interacts directly with MHC class II molecules on the surface of the antigen-presenting cell using its extracellular domain. The extracellular domain adopts an immunoglobulin-like beta-sandwich with seven strands in 2 beta sheets, in a Greek key topology. CD4 has also been shown to interact with SPG21, Lck and Protein unc-119 homolog. CD4 is a primary receptor used by HIV-1 to gain entry into host T cells. HIV infection leads to a progressive reduction of the number of T cells possessing CD4 receptors. Therefore, medical professionals refer to the CD4 count to decide when to begin treatment for HIV-infected patients.