T CELL RECEPTOR BINDING TO ALWGPDPAAA, DERIVED FROM HUMAN PRE-PRO INSULIN (PPI) PROTEIN

摘要

The present invention provides a T cell receptor (TCR) having the property of binding to 5 ALWGPDPAAA (derived from human pre-pro insulin (PPI) protein) HLA-A*02 complex and comprising a TCR alpha chain variable domain and a TCR beta chain variable domain. The alpha chain variable domain comprises an amino acid sequence that has at least 90% identity to the sequence of amino acid residues 1-112 of SEQ ID No: 2 with at least one specified substitution and/or insertion therein. The beta chain variable domain comprises an amino acid sequence that10 has at least 90% identity to the sequence of amino acid residues 1-116 of SEQ ID No: 3 with at least one specified substitution therein. Also provided are nucleic acids encoding the TCR and cells engineered to present the TCR. Therapeutic agents based on TCRs of the invention can be used for the purpose of delivering immunosuppressive agents to beta cells in order to prevent their destruction by CD8* T15 cells.