Recombinant human progenitor cells, engineered human thymocytes, and engineered human T cells

A method of producing an engineered thymocyte or an engineered T cell which comprises

• spectratyping-based cloning to obtain a nucleic acid molecule which encodes a human T cell receptor specific for a virus or an epitope thereof;
• transducing a human hematopoietic stem cell with a vector containing the nucleic acid molecule to give a recombinant progenitor cell;
• and
• differentiating or developing the recombinant progenitor cell into the engineered thymocyte by subjecting the recombinant progenitor cell to a thymus tissue, and then optionally maturing the engineered thymocyte into the engineered T cell, and
• wherein the spectratyping-based cloning comprises
• obtaining peripheral blood mononuclear cells from a subject infected with the virus and dividing the peripheral blood mononuclear cells into a first portion and a second portion;
• culturing the first portion with the virus or the epitope thereof;
• spectratyping the TCR α-genes and TCR β-genes in the first portion to obtain a first fingerprint;
• spectratyping the TCR α-genes and TCR β-genes in the second portion to obtain a second fingerprint;
• selecting a TCR α-gene and a TCR β-gene in the first portion which are not present in the second portion;
• and
• recombinantly joining the selected TCR α-gene and TCR β-gene to give the nucleic acid molecule.