Mhc binding peptide oligomers and methods of use
OwnerJack L. Strominger, Kirsten Falk +1inventors
InventorsJACK L. STROMINGER, KIRSTEN FALK, OLAF ROTZSCHKE
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Abstract
Disclosed are oligomers comprising at least two MHC binding peptides joined by a flexible molecular linker. The MHC binding peptides can be MHC class I binding peptides or MHC class II binding peptides. Also disclosed is an oriented cloning method for producing such oligomers. The disclosed oligomers can be used, for example, in connection with methods for specifically activating or inhibiting the activation of CD4+ or CD8+ T cells. Such methods provide therapeutic approaches for the treatment of tumors, autoimmune disorders, allograft rejection and allergic reactions.
Claims88
An MHC binding peptide oligomer comprising at least two MHC binding peptides covalently joined by a flexible molecular linker.
Use of an MHC binding peptide oligomer in a composition for specifically activating a CD8+ T cell toward a cell presenting a predetermined antigenic peptide in association with a predetermined MHC class I molecule, wherein said specific activation is achieved by:
- (a) providing an MHC binding peptide oligomer comprising at least two agonistic MHC class I binding peptides covalently joined by a flexible molecular linker, said MHC class I binding peptides corresponding to said predetermined antigenic peptide;
- and
- (b) contacting, under physiological conditions, a cell bearing said MHC class I molecule on its cell surface with the oligomer of step (a).
A use as in claim 16 wherein said flexible molecular linker is produced in vitro by chemical synthetic techniques.
Use of an MHC binding peptide oligomer in a composition for specifically inhibiting activation of a CD8+ T cell toward a cell presenting a predetermined antigenic peptide in association with a predetermined MHC class I molecule, wherein said specific inhibition is achieved by:
- (a) providing an MHC binding peptide oligomer comprising at least two non-aginostic MHC class I binding peptides covalently joined C-terminus to C-terminus by a flexible molecular linker, said MHC class I binding peptides corresponding to said predetermined antigenic peptide;
- and
- (b) contacting, under physiological conditions, a cell bearing said MHC class I molecules on its cell surface with the oligomer of step (a).
Use of an MHC binding peptide oligomer in a composition for activating a CD4+ T cell toward a cell presenting a predetermined antigenic peptide in association with a predetermined MHC class II molecule, wherein said activation is achieved by:
- (a) providing an MHC binding peptide oligomer comprising at least two agonistic MHC class II binding peptides covalently joined by a flexible molecular linker, said MHC class II binding peptides comprising said predetermined antigenic peptide;
- and
- (b) contacting, under physiological conditions, a cell bearing said MHC class II molecules on its cell surface with the oligomer of step (a).
Use of an MHC binding peptide oligomer in a composition for specifically inhibiting activation of a CD4+ T cell toward a cell presenting a predetermined antigenic peptide in association with a predetermined MHC class II molecule, wherein said specific inhibition is achieved by:
- (a) providing an MHC binding peptide oligomer comprising at least two non-agonistic MHC class II binding peptides covalently joined by a flexible molecular linker;
- and
- (b) contacting, under physiological conditions, a cell bearing said MHC class II molecules on its cell surface with the oligomer of step (a).
Use of a DNA sequence encoding an MHC binding peptide oligomer in a medicament for genetic immunization against a predetermined pathogen, wherein said immunization is achieved by:
- (a) providing said DNA sequence encoding an MHC binding peptide oligomer comprising at least two immunogenic MHC binding peptides derived from said pathogen covalently joined by a flexible molecular linker in an expression vector capable of replication and expression in mammalian cells;
- and
- (b) introducing the expression vector of step (a) into the cells of an individual to be immunized.
Use of an MHC binding peptide oligomer in a medicament for eliminating tumor cells from an individual, wherein said elimination is achieved by:
- (a) providing an MHC binding peptide oligomer comprising at least two agonistic, tumor-specific MHC binding peptides covalently joined by a flexible molecular linker;
- and
- (b) contacting under physiological conditions, a cell bearing MHC molecules on its cell surface with the oligomer of step (a).
Use of an MHC binding peptide oligomer in a composition for specifically inhibiting activation of a T cell by a predetermined antigenic peptide in association with a predetermined MHC molecule, wherein said specific inhibition is achieved by:
- (a) providing an MHC binding peptide oligomer comprising at least two of said antigenic peptides covalently joined by a flexible molecular linker;
- and
- (b) contacting, under physiological conditions, a cell bearing said MHC molecule on its cell surface with the oligomer of step (a) at a concentration sufficient for the induction of high zone tolerance.
Use of an MHC binding peptide oligomer for producing an immunomodulatory composition, comprising:
- (a) identifying an MHC binding peptide;
- and
- (b) preparing an MHC binding peptide oligomer comprising at least two copies of the MHC binding peptide of step (a) covalently joined by a flexible molecular linker.
Dependencies are inferred from the claim text.