Disulfide trap MHC class I molecules and uses therefor

US8992937B2 · kind B2 · utility

Assignee

• Washington University · US

Inventors

• Ted Hansen · Chesterfield, US
• Daved Fremont · Chesterfield, US
• Janet Connolly · North Potomac, US
• Lonnie Lybarger · Tucson, US
• Michael Miley · Cary, US
• Vesselin Mitaksov · Ballwin, US
• Steven Truscott · Royal Oak, US

Key dates

• Filing date: Aug 28, 2007
• Grant date: Mar 31, 2015
• Expiry date: Mar 9, 2032

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A disulfide trap, comprising an antigen peptide covalently attached to an MHC class I heavy chain molecule by a disulfide bond extending between two cysteines, is disclosed. In some configurations, a disulfide trap, such as a disulfide trap single chain trimer (dtSCT), can comprise a single contiguous polypeptide chain. Upon synthesis in a cell, a disulfide trap oxidizes properly in the ER, and can be recognized by T cells. In some configurations, a peptide moiety of a disulfide trap is not displaced by high-affinity competitor peptides, even if the peptide binds the heavy chain relatively weakly. In various configurations, a disulfide trap can be used for vaccination, to elicit CD8 T cells, and in multivalent MHC/peptide reagents for the enumeration and tracking of T cells. Also disclosed are nucleic acids comprising a sequence encoding a disulfide trap. Such nucleic acids, which can be DNA vectors, can be used as vaccines.