"Technologies for T cell visualisation and T cell depletion/enrichment are steadily making their way into the clinic and developments seem dictated by availability and reliability of the peptide-Major Histocompatibility Complex (pMHC) reagents used. A bottleneck has always been the laborious process of expression, refolding and purification of individual pMHCs. Recently, conditional MHC technology, pioneered in the host laboratory, solved this problem in part by enabling high-throughput loading of one MHC allele with a wide panel of peptide ligands. However, the rapid, parallel generation of a variety of MHC alleles is still a major hurdle. Therefore, proposed research aims at the total chemical synthesis of conditional MHC platforms, to make high-throughput generation of different MHC alleles reality. Recent advances in solid phase peptide synthesis (SPPS) have now enabled the generation of long polypeptides and even small proteins. This proposal aims to use SPPS rather than biological expression systems for total protein synthesis. The major advantage of using chemical techniques for protein synthesis is (1) that it allows the facile introduction of (non-natural) amino acids with functionalities that stabilise the protein by enhanced H-bonding, intrastrand crosslinking or intramolecular cross-linking (cyclisation) and that enable immobilisation or conjugation, (2) that protein yields are higher, and (3) that it simplifies the controlled generation of GMP grade proteins for biomedical use.The outcomes of this project will benefit the development of adoptive T cell therapy and will enable epitope scans through entire genomes of emerging pathogens (e.g. pandemic H1N1 Influenza), thus contributing to vaccine development."