Immune recognition motifs

Abstract

The present invention provides methods and systems for identifying and classifying epitopes and use of that information to analyze proteins and peptides within proteins, especially potential epitopes, and to use the information to design synthetic peptides and proteins, analyze biopharmaceutical proteins, and diagnose autoimmune conditions. Peptides which are bound in MHC grooves comprise two sets of amino acids: those that face inwards into the groove and determine the binding affinity to the MHC molecule (the groove exposed motifs or GEM) and those which do not interact with the groove but rather are on the obverse side exposed outwardly to the T-cells (the T-cell exposed Motifs or TCEM). The present invention utilizes information related to the identity and physiochemical characteristics of the GEM and TCEM.

What is claimed is: 
     
         1 . A method for reducing the count of T cell clones in a subject in need thereof, comprising:
 identifying a T cell exposed motif of interest;   synthesizing a peptide that comprises the T cell exposed motif of interest; and   administering said peptide to said subject so that the count of T cells that binds to the peptide comprising the T cell exposed motif of interest is reduced.   
     
     
         2 . The method of  claim 1 , wherein the method further comprises the step of determining the MHC alleles of the subject in which it is desired to deplete the T cell clone. 
     
     
         3 . The method of  claim 2 , wherein the peptide comprising the T cell exposed motif of interest binds to one or more allele of the subject's MHC molecules with a binding affinity of greater than 1×10 7 M −1 . 
     
     
         4 . The method of  claim 2 , wherein the peptide comprising the T cell exposed motif of interest binds to one or more allele of the subject's MHC molecules with a binding affinity of greater than 1×10 8 M −1 . 
     
     
         5 . The method of  claim 2 , wherein the peptide comprising the T cell exposed motif of interest binds to one or more allele of the subject's MHC molecules with a binding affinity of greater than 1×10 9 M −1 . 
     
     
         6 . The method of  claim 1 , wherein the peptide comprising the T cell exposed motif further comprises a cytotoxin in operable association with the peptide. 
     
     
         7 . The method of  claim 6 , wherein the cytotoxin is a radionuclide molecule. 
     
     
         8 . The method of  claim 7 , wherein the radionuclide is an iodine isotope. 
     
     
         9 . The method of  claim 7 , wherein the radionuclide is an alpha emitter. 
     
     
         10 . The method of  claim 9 , wherein the alpha emitter is selected from the from the group comprising Bismuth-213, Actinium-225 and Lead-212. 
     
     
         11 . The method of  claim 7 , wherein the radionuclide is an Auger electron emitter. 
     
     
         12 . The method of  claim 11 , wherein the Auger electron emitter is selected from the group consisting of Gadolinium-67, Technicium-99, Indium-111, Iodine-123, Iodine-125, and Tellurium-201. 
     
     
         13 . The method of  claim 6 , wherein the cytotoxin is a positron emitter. 
     
     
         14 . The method of  claim 13 , wherein the positron emitter is selected from the group consisting of Carbon-11, Nitrogen-13, Fluorine-18, Iron-52, Iodine-124, Yttrium-86, Gadolium-68 and Arsenic-72. 
     
     
         15 . The method of  claim 6 , wherein the cytotoxin is a cytokine. 
     
     
         16 . The method of  claim 6 , wherein the cytotoxin is selected from the group consisting of an RNAse, a phospholipase, a membrane active peptide, and a diphtheria toxin. 
     
     
         17 . The method of  claim 1 , wherein the peptide comprising the T cell exposed motif further comprises a metallic particle in operable association therewith. 
     
     
         18 . The method of  claim 1 , wherein the peptide comprising the T cell exposed motif further comprises a MHC molecule subunit in operable association therewith. 
     
     
         19 . The method of  claim 7 , wherein the peptide comprising the T cell exposed with a cytotoxin in operable association with the peptide further comprises a MHC molecule subunit in operable association therewith. 
     
     
         20 . The method of  claim 19 , further comprising subjecting said subject to targeted electro-magnetic radiation. 
     
     
         21 . The method of  claim 19 , wherein the metallic particle is selected from the group consisting of a gold particle and a ferritin particle. 
     
     
         22 . The method of  claim 1 , wherein amino acids in said peptide comprising said T cell exposed motif are substituted with alternative amino acids, without alternation of the amino acids in said T cell exposed motif, to achieve a desired binding affinity to a MHC allele of said subject. 
     
     
         23 . The method of  claim 1 , wherein said MHC allele is a MHC I. 
     
     
         24 . The method of  claim 1 , wherein said MHC is a MHC II. 
     
     
         25 . The method of  claim 1 , wherein the subject has cancer. 
     
     
         26 . The method of  claim 24 , wherein the cancer is selected from the group consisting of lymphoma, leukemia and myeloma. 
     
     
         27 . The method of  claim 1 , wherein the subject has an autoimmune disease. 
     
     
         28 . The method of  claim 26 , wherein the autoimmune disease is selected from the group consisting of multiple sclerosis, systemic lupus erythematosis, myasthenia gravis, rheumatoid arthritis, Alzheimer's disease, diabetes, and Parkinson's disease. 
     
     
         29 . The method of  claim 1 , wherein the T cell exposed motif occurs more frequently than 1 in 1024 of the T cell exposed motifs in a reference database comprising at least 40,000 human immunoglobulin variable regions. 
     
     
         30 . The method of  claim 1 , wherein the T cell exposed motif occurs less frequently than 1 in 1024 of the T cell exposed motifs in a reference database comprising at least 40,000 human immunoglobulin variable regions. 
     
     
         31 . The method of  claim 1 , wherein the T cell exposed motif occurs less frequently than 1 in 4 million of the T cell exposed motifs in a reference database comprising at least 10 million human immunoglobulin variable region complementarity determining region sequences. 
     
     
         32 . The method of  claim 1 , wherein the T cell exposed motif occurs more frequently than the mean frequency of the T cell exposed motifs in a reference database comprising all T cell exposed motifs in at least 20,000 human proteome proteins. 
     
     
         33 . The method of  claim 1 , wherein the T cell exposed motif is not present in a reference database comprising all T cell exposed motifs in 20,000 human proteome proteins. 
     
     
         34 . The method of  claim 1 , wherein the peptide comprising the T cell exposed motif of interest is delivered to dendritic cells ex vivo and said dendritic cell are then administered to said subject.