Title: Structural Basis of Metal Allergies

Presenter: Dr. Shaodong Dai

University: Integrated Department of Immunology, National Jewish Health & University of Colorado School of Medicine

Time: 10:00-11:00, July 10, 2013

Venue: Room A203, Institute of Microbiology, Chinese Academy of Sciences

Abstract: T cells play a central role in adaptive immune responses. T cell activation is initiated when T cell receptors (TCRs) interact with the antigens presented by major histocompatibility complex proteins (MHC) on antigen presenting cells. T cells bearing receptors made of and chains usually recognize antigen in the form of peptides bound to MHC (pMHC). However, metal and other small molecules can be unconventional components of TCR ligands and, in this form, can cause some of the most common immunity-related diseases, allergies to metal ions such as Ni2+ and lung diseases, such as CBD. Metal ions may incorporate into pMHC to form TCR ligands in different ways. We recently identified two different metal binding sites on the surface of pMHC. First, a Be2+ binding site was discovered on an allele of a human MHCII protein, HLA-DP2. This site is highly acidic, and its presence on DP2 is in agreement with the strong association of CBD with HLA alleles bearing 69E. Our data suggest that the Be2+ is buried in the P5-P7 pocket of HLA-DP2, and creates a neoantigen by changing the conformation of a self-peptide(s) bound to DP2. Secondly, a Ni2+ ion coordination site was discovered on human MHCII, HLA-DR52c. In contrast to Be2+, Ni2+ is located on top of the self-peptide where it may interact directly with Ni2+ specific TCRs.  However, like Be2+ on DP2, Ni2+ is located in the P5-P7 region of the MHCII/peptide complex. Therefore, we identified common binding feature of metal antigen. This feature can be used for the development of drugs.