Project Summary/Abstract – Core B Core B will provide two technologies for the three Projects that are difficult to import into individual laboratories. 1) The CD4+ T cells that will studied in these Projects recognize self-peptides that have bound to a class II major histocompatibility molecule (MHCII). In recent T cell research fluorescently labeled multimerized MHCII molecules uniformly occupied by a single antigenic peptide (“tetramers”) have become standard reagents for tracking antigen-specific T cells in vivo. However, producing these tetramers has been difficult and standard protocols have not been generally available. The problem has been exacerbated in autoimmune diseases such as type-1 diabetes (T1D) because the important peptide-MHCII complexes often have usual, unstable conformations. Over a number of years the personnel in Core B have solved many of these problems and made many homogeneous MHCII tetramers including some containing the major antigens of T1D. The Core will begin by making a standard set of MHCII tetramers for distribution to the three Projects. As new important peptides are discover in the courses of these studies, new tetramers will be added to the Core. 2) Understanding how the recognition of self-peptide-MHCII complexes differs from the recognition conventional foreign peptide-MHCII complexes has been hampered by a limited set for detailed structures of the interacting molecules. This Core begins a group with many years of experience in X- ray crystallography and TCR and MHCII expression to bear on this problem. They will pursue the structures of the novel peptide-MHC complexes to emerge in the three projects and of the relevant TCRs bound to these complexes.