amino acids. Full length IFN-γ is 143 amino acids long, the models are 126 amino acids long. Affinity for heparan sulfate resides solely within the deleted sequence of 17 amino acids. Within this sequence of 17 amino acids lie two clusters of basic amino acids termed D1 and D2, respectively. Heparan sulfate interacts with both of these clusters. In the absence of heparan sulfate the presence of the D1 sequence increases the rate at which IFN-γ-receptor complexes form. Interactions between the D1 cluster of amino acids and the receptor may be the first step in complex formation. By binding to D1 HS may compete with the receptor and prevent active receptor complexes from forming. The biological significance of heparan sulfates interaction with IFN-γ is unclear; however, binding of the D1 cluster to HS may protect it from proteolytic cleavage. Signaling IFN-γ binds to the type II cell-surface receptor, also known as the IFN-gamma receptor (IFNGR) which is part of the class II cytokine receptor family. The IFNGR is composed of two subunits: the IFNGR1 and IFNGR2. IFNGR1 is associated with JAK1 and IFNGR2 is associated with JAK2. Upon IFN-γ binding the receptor, IFNGR1 and IFNGR2 undergo conformational changes that result in the autophosphorylation and activation of JAK1 and JAK2. This leads to a signaling cascade and eventual transcription of target genes. The expression of 236 different genes has been linked to type II IFN-mediated signaling. The proteins expressed by type II IFN-mediated signaling are primarily involved in promoting inflammatory immune responses and regulating other cell-mediated immune responses, such as apoptosis, intracellular IgG trafficking, cytokine signaling and production, hematopoiesis, and cell proliferation and differentiation. JAK-STAT pathway One key pathway triggered by IFN-γ binding IFNGRs is the Janus Kinase and Signal Transducer and Activator of Transcription pathway, more commonly referred to as the JAK-STAT pathway. In the JAK-STAT pathway, activated JAK1 and JAK2 proteins regulate the phosphorylation of tyrosine in STAT1 transcription factors. The tyrosines are phosphorylated at a very specific location, allowing activated STAT1 proteins to interact with each other come together to form STAT1-STAT1 homodimers. The STAT1-STAT1 homodimers can then enter the cell nucleus. They then initiate transcription by binding to gamma interferon activation site (GAS) elements, which are located in the promoter region of interferon-γ stimulated genes (ISGs) that express for antiviral effector proteins, as well as positive and negative regulators of type II IFN signaling pathways. The JAK