MHC multimers in borrelia diagnostics and disease
Novel compounds carrying ligands capable of binding to counter receptors on relevant target cells are disclosed. The compounds possess a number of advantageous features, rendering them very suitable for a wide range of applications, including use as detection systems, detection of relevant target cells as well as a number of other methods. In particular, novel MHC complexes comprising one or more MHC molecules containing one or more Borrelia derived peptides are disclosed. The possibility of presenting to the target cells a plurality of MHC-peptide complexes makes the MHC complexes according to the present invention an extremely powerful tool e.g. in the field of therapy and diagnosis. The invention generally relates to the sample-mounted use of MHC complexes and MHC multimers. Also comprised by the invention is the field of therapy and vaccine, including therapeutic/vaccine methods and therapeutic/vaccine compositions.
1. An isolated MHC multimer comprising (a-b-P)n, wherein n>1 and P is a peptide derived from a Borrelia Decorin Binding Protein A,
wherein a is at least the extracellular portion of an HLA*02 heavy chain and b is β2 microglobulin,
wherein a and b together form a functional MHC complex encoded by an HLA-A*02 allele, whereto the peptide P is bound, forming a MHC peptide complex,
wherein the HLA*02 allele is selected from the group consisting of HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0211, and HLA-A*0216,
wherein each MHC peptide complex of said MHC multimer is associated with one or more multimerization domains, with the proviso that the one or more multimerization domains is not a cell, and
wherein in each MHC peptide complex, the sequence of P is selected from the group consisting of SEQ ID NOS: 5751 (GIYDLILNA), 5655 (TLLASLLAA), and 5767 (GMQGMKQAV).
2. A method for generating the isolated MHC multimer according to claim 1 , said method comprising the steps of
i) providing one or more peptides P;
ii) providing one or more functional MHC complexes,
iii) providing one or more multimerization domains, and
iv) contacting or reacting the one or more peptides P and the one or more functional MHC complexes and the one or more multimerization domains simultaneously or sequentially, in any order, thereby obtaining MHC multimers according to the present invention.
3. A composition comprising a plurality of isolated MHC multimers according to claim 1 , wherein the isolated MHC multimers are identical or different, and a carrier.
4. A kit comprising an isolated MHC multimer according to claim 1 , or the composition according to claim 3 , and at least one additional component.
5. A vaccine comprising one or more isolated MHC multimers according to claim 1 .
6. The kit according to claim 4 , wherein said at least one additional component is a positive control.
7. The kit according to claim 4 , wherein said at least one additional component is instructions for use.
8. The isolated MHC multimer according to claim 1 , wherein said one or more multimerization domains comprise a soluble polysaccharide carrier molecule.
9. The isolated MHC multimer according to claim 1 , wherein said MHC multimer is a soluble MHC multimer.
10. The isolated MHC multimer according to claim 1 , wherein the one or more multimerization domains comprise an isolated cell membrane or isolated lipid bilayer.
11. The isolated MHC multimer according to claim 1 , wherein each P is SEQ ID NO 5751.
12. The isolated MHC multimer according to claim 1 , wherein said one or more multimerization domains is selected from the group consisting of scaffolds, carriers, organic molecules and substituted organic molecules, membranes, liposomes or micelles, polymers, polysaccharides, dextran moieties, IgG domains, coiled-coil polypeptide structures, DNA duplexes, nucleic acid duplexes, PNA-PNA, PNA-DNA, DNA-RNA, avidins, streptavidins, antibodies, small organic molecules, proteins, a solid support, and biological polymers.