Recombinant t-cell receptor ligands with covalently bound peptides
AssigneeOregon Health & Science University
InventorGregory G. Burrows
Life of this patent
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Abstract
Disclosed herein are stable complexes including an MHC class I or MHC class II recombinant T cell receptor ligand RTL polypeptide covalently linked to an antigenic determinant by a disulfide bond. Also disclosed are methods of making such compositions and methods of use, for example to treat or inhibit a disorder, for example, an autoimmune disorder.
Claims24
A composition comprising:
- an isolated recombinant MHC polypeptide comprising covalently linked first and second domains, wherein:
- the first domain is a mammalian MHC class II β1 domain and the second domain is a mammalian MHC class II α1 domain and wherein the amino terminus of the second domain is covalently linked to the carboxyl terminus of the first domain and wherein the MHC class II molecule does not include an α2 or a β2 domain;
- or
- the first domain is a mammalian MHC class I α1 domain and the second domain is a mammalian MHC class I α2 domain, and wherein the amino terminus of the second domain is covalently linked to the carboxyl terminus of the first domain and wherein the MHC class I molecule does not include an α3 domain;
- and
- an antigenic determinant covalently linked to the first domain of the recombinant MHC polypeptide by a disulfide bond.
A method of treating or inhibiting type I diabetes in a subject comprising administering to the subject an effective amount of a composition comprising an isolated recombinant MHC polypeptide comprising covalently linked first and second domains, wherein the first domain is a mammalian MHC class II β1 domain and the second domain is a mammalian MHC class II α1 domain and wherein the amino terminus of the second domain is covalently linked to the carboxyl terminus of the first domain and wherein the MHC class II molecule does not include an α2 or a β2 domain and an antigenic determinant covalently linked to the first domain of the recombinant MHC polypeptide by a disulfide bond, thereby treating or inhibiting type I diabetes in the subject.
A method of producing a composition, comprising:
- contacting an antigenic determinant with an isolated recombinant MHC polypeptide comprising covalently linked first and second domains, wherein:
- the first domain is a mammalian MHC class II β1 domain and the second domain is a mammalian MHC class II α1 domain and wherein the amino terminus of the second domain is covalently linked to the carboxyl terminus of the first domain and wherein the MHC class II molecule does not include an α2 or a β2 domain;
- or
- the first domain is a mammalian MHC class I α1 domain and the second domain is a mammalian MHC class I α2 domain, and wherein the amino terminus of the second domain is covalently linked to the carboxyl terminus of the first domain and wherein the MHC class I molecule does not include an α3 domain;
- and
- under conditions sufficient for a disulfide bond to form between the antigenic determinant and the recombinant MHC polypeptide, thereby producing the composition.
Dependencies are inferred from the claim text.