MHC peptide complexes and uses thereof in infectious diseases
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 are disclosed. The affinity and specificity of the MHC-peptide complexes are surprisingly high. 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 field of therapy, including therapeutic methods and therapeutic compositions. Also comprised by the present invention is the sample-mounted use of MHC complexes and MHC multimers.
1. An isolated MHC multimer comprising (a-b-P) n ,
wherein n>1,
wherein a and b together form a functional MHC protein which is bound to the peptide P, forming a MHC peptide complex,
wherein each MHC peptide complex of a MHC multimer is associated with one or more multimerization domains,
wherein in at least one MHC peptide complex, P consists of the amino acid sequence FTKEDTITV (SEQ ID NO 51130).
2. The MHC multimer according to claim 1 , wherein the MHC multimer comprises MHC class 1 molecules.
3. The MHC multimer according to claim 1 , wherein the MHC multimer comprises MHC class 2 molecules.
4. The MHC multimer according to claim 1 , wherein the MI-IC multimer comprises one or more covalently or non-covalently attached labels, and wherein said one or more labels can be selected from the group consisting of fluorescent labels, fluorophores, enzymes, radioisotopes, chemiluminescent labels, dyes, bioluminescent labels, metal particles, haptens, polymers, and antibodies.
5. The MHC multimer according to claim 1 , wherein the one or more multimerization domains can be selected from the group consisting of scaffolds, carriers, optionally 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, cells, cell-like structures, solid support, molecules, biological polymers, and self-assembling multimeric structures.
6. The MHC multimer according to claim 1 , wherein the one or more multimerization domains comprises one or more biological cells.
7. The MHC multimer according to claim 1 , wherein the MHC multimer comprises both MHC class 1 and MHC class 2 molecules.
8. A composition comprising a plurality of MHC multimers according to claim 1 and a carrier, wherein the MHC multimers are identical.
9. A composition comprising a plurality of MHC multimers according to claim 1 and a carrier, wherein the MHC multimers are different.
10. A kit comprising a MHC multimer according to claim 1 , a positive control, and/or instructions for use.
11. A kit comprising a composition according to claim 8 , a positive control, and/or instructions for use.
12. A kit comprising a composition according to claim 9 , a positive control, and/or instructions for use.
13. A vaccine reagent comprising a MI-IC multimer according to claim 1 .