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,
wherein (a-b-P) is the MHC peptide complex formed when the peptide P is bound to the functional MHC protein,
wherein each MHC peptide complex of the MHC multimer is associated with one or more multimerization domains 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, a solid support, and biological polymers, with the proviso that the one or more multimerization domains is not a cell,
wherein each MHC protein is an MHC class I molecule encoded by an HLA-A*02 allele, and
wherein in at least one MHC peptide complex, the sequence of P originates from a Borrelia OspC antigen, is capable of binding said MHC class I molecule encoded by an HLA-A*02 allele, and is selected from the group consisting of SEQ ID NOS:49735, 49739, 49779, 49795, 49921, and 49937.
2. The isolated MHC multimer according to claim 1 , wherein n is in the range from 8 to 25.
3. The isolated MHC multimer according to claim 1 , wherein n>10.
4. The isolated MHC multimer according to claim 1 , wherein the MHC 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. A composition comprising a plurality of MHC multimers according to claim 1 and a carrier, wherein the MHC multimers are identical.
6. A composition comprising a plurality of MHC multimers according to claim 1 and a carrier, wherein the MHC multimers are different.
7. A kit comprising a MHC multimer according to claim 1 , a positive control, and/or instructions for use.
8. The isolated MHC multimer according to claim 1 , wherein the HLA*02 allele is selected from the group consisting of HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0206, HLA-A*0211, HLA-A*0212, HLA-A*0216, HLA-A*0217, HLA-A*0219, and HLA-A*0250.