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 for detection of Borrelia specific CD8+ T cells, the 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 an MHC multimer is associated with one or more multimerization domains,
wherein in at least one MHC peptide complex, the sequence of P originates from a Borrelia antigen.
2 . The isolated MHC multimer according to claim 1 , wherein in at least one MHC peptide complex, P is an 8-mer, 9-mer, 10-mer, 11-mer or 12-mer.
3 . The isolated MHC multimer according to claim 1 , wherein in at least one MHC peptide complex, P is capable of binding to MHC class I.
4 . The isolated MHC multimer according to claim 1 , wherein in at least one MHC peptide complex, the sequence of P is contained in a Borrelia burgdorferi antigen and is capable of interacting with one or more MHC class I molecules.
5 . The isolated MHC multimer according to claim 1 , wherein in at least one MHC peptide complex, the sequence of P is contained in a Borrelia afzelii antigen and is capable of interacting with one or more MHC class I molecules.
6 . The isolated MHC multimer according to claim 1 , wherein in at least one MHC peptide complex, the sequence of P is contained in a Borrelia garinii antigen and is capable of interacting with one or more MHC class I molecules.
7 . The isolated MHC multimer according to claim 1 , wherein in at least one MHC peptide complex, the sequence of P is contained in Osp C derived from Borrelia afzelli and is capable of interacting with one or more MHC class I molecules.
8 . The isolated MHC multimer according to claim 1 , wherein in at least one MHC peptide complex, the sequence of P is contained in OspA derived from Borrelia burgdorferi and is capable of interacting with one or more MHC class I molecules.
9 . The isolated MHC multimer according to claim 1 , wherein in at least one MHC peptide complex, the sequence of P is contained in FlaB derived from Borrelia garinii and is capable of interacting with one or more MHC class I molecules.
10 . A method for immune monitoring one or more Borrelia infections comprising the following steps:
i) providing the MHC multimer according to claim 1 , or the individual components thereof,
ii) providing a population of T cells, and
iii) measuring the number, activity or state of T cells specific for said MHC multimer, thereby immune monitoring said one or more Borrelia infections.
11 . A method for diagnosing one or more Borrelia infections comprising the following steps:
i) providing the MHC multimer according to claim 1 , or individual components thereof,
ii) providing a population T cells, and
iii) measuring the number, activity or state of T cells specific for said MHC multimer, thereby diagnosing said one or more diseases.
12 . A method for isolation of one or more Borrelia antigen specific T cells, said method comprising the steps of:
i) providing the MHC multimer according to claim 1 , or individual components thereof,
ii) providing a population of T cells, and
iii) isolating T cells specific for said MHC multimer.