Chapter 4 │ Page 120 interactions between NTP and cancer cells, with regard to NK cell recognition. This data can provide the groundwork towards rationally designed combination of NTP with exciting and newly developed immune therapies to improve treatment e iciency and accelerate the clinical introduction of this appealing agent. 2. MATERIAL AND METHODS 2.1. Preparation Of The Model Systems Figure 1 illustrates the two NK cell inhibiting ligand-receptor protein complexes computationally investigated in this study, i.e., HLA-Cw4 – KIR2DL1 (left) and HLAE – NKG2A/CD94 (right). MHC-I molecules consist of a variable α-chain that presents an intracellular peptide (shown in red), and the smaller β2-microglobulin (β2M, shown in orange) [36]. HLA-E is recognized by the NK cell inhibiting receptor NKG2A, which forms a heterodimer with CD94 in order to become a functional receptor. In contrast to HLA-E, which has a low degree of polymorphism [37], HLA-A, B and C are extremely diverse, as is the group of NK cell receptors that bind to them, i.e. KIR. As discussed by Parham [38], HLA-C is the most important classical MHC-I protein in humans. In addition, of the group of inhibitory KIRs that recognize the various types of HLA-C, KIR2DL1 is the most inhibitory to NK cells. Figure 1: Schematic representation of the two protein complexes computationally studied, i.e., HLA-Cw4 – KIR2DL1 (left) and HLA-E – NKG2A/CD94 (right).
RkJQdWJsaXNoZXIy MTk4NDMw