Structural insight into DRB1-antigen-TCR interactions. (A) Peptides of vimentin (UniProt: P08670, VIME_HUMAN, 59-71), EBV DNA polymerase (UniProt: P03198, DPOL_EBVB9, 628-641), MBP (UniProt: P02686, MBP_HUMAN, 217-231) at the HLA binding site based on the alignment of crystal structures of DRB1*15:01-DRA*01:01/MBP (217-231) (PDB: 1BX2), DRB1*14:02-DRA*01:01/vimentin (amino acid positions: 59-71, PDB:1H15), and DRB5*01:01-DRA*01:01/EBV DNA polymerase (628-641) (PDB:6ATF). The red squares indicate the peptide portions presenting with more conformational variability (in interaction with the right site of the HLA binding groove). This 3D structure has been prepared with PyMOL using the crystal structure of DRB1*15:01-DRA*01:01/MBP (PDB: 1BX2). (B) Modeled ternary structure of HLA-Antigen-TCR-CD4. (C) Detail of the interaction interface in HLA-antigen-TCR. The 3 antigenic structures are aligned as shown above. The risk amino acid pattern within the right side of the binding groove interacts with a more variable antigenic portion that contacts directly with the TCR β chain (software PyMOL). EBV, Epstein-Barr virus; MHC, major histocompatibility complex.