Fig. 2.

IDH1 is a cytosolic protein with enzymatic activity. A point mutation leads t a single amino acid exchange (R132H), resulting in a neomorphic enzymatic function, the production of R-2-HG. IDH1(R132H) is processed in the endosomes and lysosomes within tumor cells and APCs that have taken up the protein from necrotic and apoptotic tumor cells, from where the epitope pIDH1R132H is loaded onto MHC class II. This makes it accessible for IDH1(R132H-specific CD4+ T cells. Amino acid exchange to histidine is shown in red