Inventors:
Ted H. Hansen - St. Louis MO, US
David H. Fremont - St. Louis MO, US
Janet Connolly - St. Louis MO, US
Lonnie Lybarger - Tuson AZ, US
Michael Miley - Durham NC, US
Vesselin Mitaksov - Manchester MO, US
Steven Truscott - St. Louis MO, US
International Classification:
A61K 39/12
C07K 14/00
C12N 5/00
C12N 5/02
A61P 35/04
A61K 35/56
C07K 1/13
C07H 21/04
US Classification:
4242041, 530350, 435325, 536 2372, 530403, 435373, 424 937
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.