Methods of MHC class II epitope mapping, detection of autoimmune T cells and antigens, and autoimmune treatment

A method for identifying an MHC class II epitope of a predetermined polypeptide antigen, comprising;

• preparing a library of at least two peptide pools, each peptide pool comprising at least two peptides, the peptides comprising a fragment of the predetermined polypeptide antigen and sharing a region of overlapping amino acid sequence identity with at least one other peptide in the library;
• forming pools of MHC class II/peptide tetramers from the pools of peptides and soluble human MHC class II molecules, each MHC class II/peptide tetramer comprising four MHC class II molecule/peptide pairs, wherein the peptides are bound to the MHC class II molecules, said forming of MHC class II/peptide tetramers comprising loading the human MHC class II molecules with the peptide pools;
• contacting the pools of MHC class II/peptide tetramers with human T cells;
• identifying at least one pool of MHC class II/peptide tetramers that binds to the T cells;
• and
• contacting T cells with MHC class II/peptide tetramers Conned with individual peptides from the pool of MHC class II/peptide tetramers that binds to the T cells to identify at least one epitope in the peptide pool.